Tens of millions of Americans who work at companies with 100 or more employees will need to be fully vaccinated against COVID-19 by Jan. 4 or get tested for the virus weekly under government rules issued today.

The new requirements, which were first previewed by President Joe Biden in September, will apply to about 84 million workers at medium and large businesses, although it is not clear how many of those employees are unvaccinated.

The Occupational Safety and Health Administration regulations will force the companies to require that unvaccinated workers test negative for COVID-19 at least once a week and wear a mask while in the workplace.

OSHA left open the possibility of expanding the requirement to smaller businesses. It asked for public comment on whether employers with fewer than 100 employees could handle vaccination or testing programs.

Tougher rules will apply to another 17 million people who work in nursing homes, hospitals and other facilities that receive money from Medicare and Medicaid. Those workers will not have an option for testing — they will need to be vaccinated.

Workers will be able to ask for exemptions on medical or religious grounds.

Biden framed the issue as a simple choice between getting more people vaccinated or prolonging the pandemic.

“While I would have much preferred that requirements not become necessary, too many people remain unvaccinated for us to get out of this pandemic for good,” he said today in a statement.

Biden said his encouragement for businesses to impose mandates and his own previous requirements for the military and federal contractors have helped reduce the number of unvaccinated Americans over 12 from 100 million in late July to about 60 million now.

Those measures, he said, have not led to mass firings or worker shortages, adding that vaccines have been required before to fight other diseases.

OSHA said companies that fail to comply with the regulations could face penalties of nearly $14,000 per violation.

It was unclear how OSHA planned to enforce the rules: Even counting allied regulators at the state level, the agency has only 1,850 inspectors to oversee 130 million workers at 8 million workplaces. A senior administration official said OSHA will target companies if it gets complaints.

The release of the rules followed weeks of regulatory review and meetings with business groups, labor unions and others. The regulations form the cornerstone of Biden’s most aggressive effort yet to combat the spread of COVID-19, which has killed more than 740,000 people in the U.S.

OSHA drafted the rules under emergency authority meant to protect workers from an imminent health hazard. The agency estimated that the vaccine mandate will save more than 6,500 worker lives and prevent more than 250,000 hospitalizations over the next six months.

Senior administration officials said the rules preempt conflicting state laws or orders, including those that ban employers from requiring vaccinations, testing or the wearing of face masks.

The administration will face an immediate challenge from Republican state officials who are eager to fight Biden in court and in Congress. Senate Republicans immediately launched a petition to force a vote to overturn the vaccine mandate, but with Democrats controlling the chamber, the effort is nearly certain to fail.

More than two dozen Republicans serving as state attorneys general have indicated they plan to sue, arguing that only Congress can enact such sweeping requirements under emergency authority.

Last week, 19 states sued to stop Biden’s narrower mandate that employees of federal contractors be vaccinated. That requirement was scheduled to take effect Dec. 8, but the administration said today it will be delayed until Jan. 4 to match the requirements on other large employers and health care providers.

The rules will require workers to receive either two doses of the Pfizer or Moderna vaccines or one dose of the Johnson & Johnson vaccine by Jan. 4 or be tested weekly. Employees who test positive must be removed from the workplace.

The requirements will not apply to people who work at home or outdoors.

Companies won’t be required to provide or pay for the tests, but they must give paid time off for employees to get vaccines and sick leave to recover from side effects that prevent them from working. The requirements for masks and paid time off for shots will take effect Dec. 5.

The Centers for Medicare & Medicaid Services issued a separate rule requiring vaccination for workers in 76,000 health facilities and home health care providers that get funding from the government health programs. A senior administration official said that several large private health care organizations imposed their own mandates and achieved high vaccination rates — 96% or higher — without widespread resignations.

For weeks, Biden has encouraged businesses not to wait for the OSHA rule to take effect. He has touted businesses that have already announced their own vaccine mandates and urged other companies to follow their lead.

Administration officials say those efforts are paying off, with about 70% of the nation’s adults now fully vaccinated.

Walmart, the nation’s largest private employer, said in late July it was requiring all workers at its headquarters in Bentonville, Arkansas, as well as its managers who travel within the U.S., to be vaccinated against COVID-19 by Oct. 4. But the company had stopped short of requiring shots for its frontline workers.

United Airlines required U.S. employees to get vaccinated or face termination. Only a very small number of its 67,000 workers refused to do so.

In August, Tyson Foods told its 120,000 U.S. workers that they must be vaccinated by Nov. 1. A week before that deadline, the company said 96% of its workforce was fully vaccinated.

However, some companies have expressed fea r that some vaccine-hesitant workers might quit, leaving their workforces even thinner in what is already a tight labor market.

Several large business groups complained about the timing of the mandate. Retail groups worried that the requirement could disrupt their operations during the critical Christmas shopping period. Retailers and others also said it could worsen supply chain disruptions.

The National Retail Federation suggested that the new rules are not needed because the rolling average number of new daily cases in the U.S. has fallen by more than half since September.

“Nevertheless, the Biden administration has chosen to declare an ‘emergency’ and impose burdensome new requirements on retailers during the crucial holiday shopping season,” said David French, a senior vice president for the trade group.

The number of new COVID-19 infections in the U.S. is still falling from a summer surge caused by the highly contagious delta variant, but the rate of decline has slowed in recent weeks. The 7-day moving average is down 6% from two weeks ago, at more than 76,000 new cases and 1,200 deaths per day.

The earlier mandate on federal contractors led to demonstrations by opponents, including workers at a NASA rocket engine test site in Mississippi. Some said they are immune because they contracted COVID-19. Others said vaccines violated their religious beliefs and constitutional rights.

“No one should be forced to take a medical treatment just to keep their job,” said Nyla Trumbach, an engineer at the site. “There’s years and years of experience and skill out here, and I just want anyone who’s watching to see what we stand to lose here if these people don’t keep their jobs.”