Two actors leave the soap opera ‘General Hospital’ over its vaccine mandate.

Two actors have left one of America’s most popular soap operas after declining to comply with an on-set vaccination mandate.

The actors, Steve Burton and Ingo Rademacher, were fixtures of ABC’s “General Hospital,” a long-running daytime drama set in the fictional town of Port Charles, N.Y.

About one in five American adults has not received a single dose of a coronavirus vaccine.

Mr. Burton and Mr. Rademacher were outspoken opponents of a coronavirus vaccine mandate that applied to a part of the set where actors work unmasked, known in the industry as Zone A. The mandate took effect on Nov. 1.

“Unfortunately, ‘General Hospital’ has let me go because of the vaccine mandate,” Mr. Burton, who tested positive for the virus in August and filmed his last episode on Oct. 27, said in an Instagram video on Tuesday.

“I did apply for my medical and religious exemptions and both of those were denied — which, you know, hurts,” he added. “But this is also about personal freedom to me. I don’t think anyone should lose their livelihood over this.”

Mr. Rademacher’s departure from the show was made public earlier this month. He had also refused to comply with the show’s vaccine mandate. “I will stand with you to fight for medical freedom,” he wrote in an Instagram post.

Mr. Rademacher has also been criticized on social media in recent weeks for making comments that his critics perceived to be transphobic, a suggestion he has forcefully denied.

Representatives for ABC declined to comment on the record. Publicists for the actors could not be reached for comment late Tuesday.

Other Hollywood productions have imposed similar on-set mandates, but there is no universal vaccination requirement for people who work in film and television.

“General Hospital” has been on the air since 1963. Its episodes are filmed weeks before they air.

Mr. Rademacher played the character Jasper “Jax” Jacks on the show for 25 years. In his last episode, which aired on Monday, the character said — spoiler alert — that he would be returning to Australia.

“I’m kind of on the outs with everyone in Port Charles right now,” the character said. Some fans interpreted that as a reference to the actor’s real-life tension with his castmates.

In the same episode, Mr. Burton’s character, Jason Morgan, was caught up in a tunnel collapse.

Mr. Burton said in his Instagram video on Tuesday that he hoped the show’s vaccine mandate would be lifted so that he could finish his career playing Jason Morgan.

“And if not,” he added, “I’m going to take this experience, move forward and be forever grateful.”