Nearly 600 United Airlines employees face being fired after failing to comply with the firm's Covid-19 vaccination policy.
The vast majority of its 67,000 US staff have supplied proof of vaccination, which was required by Monday.
"This was an incredibly difficult decision," its bosses said in a memo to employees.
The Chicago-based airline set out its Covid requirements for staff in August.
Its US employees had to upload proof of vaccination, or the first of two jabs, by the deadline on Monday.
The 593 workers who have refused a coronavirus vaccine and have not applied for an exemption on religious or medical grounds now face losing their jobs.
A further 2,000 employees have requested an exemption to the policy.
It previously said it would put those who are exempt on temporary, unpaid leave from 2 October. But those plans were put on hold after a lawsuit was filed by six employees challenging the policy.
Elsewhere in the US, few airlines have introduced vaccine mandates for its staff. Delta Airlines, for example, has announced a $200 (£148) monthly health insurance surcharge for those who are not jabbed.
The vaccine DOES NOT work. We have vaccinated people who get sick, who spread the disease, and who are creating variants.
On the down side, the vaccine has killed somewhere between 15,386 and 150,000 people who are DEAD. The FDA claims that there are 5 people murdered by the vaccine, for every person who is "statistically saved". And that means that other known cures are NOT ALLOWED to be tried, such known cures as Ivermectin and HQZ