Paul Bradley and Patricia Potter are returning to Holby City for its 20th anniversary.
The former EastEnders actor will reprise his role as Elliot Hope for the show's 1,000th episode, and another four eps, and Patricia's character Diane Lloyd will return from beyond the grave after she died in 2007.
Paul said: "I'm really looking forward to returning to a programme on which I spent so many happy years.
I’m really looking forward to returning to a programme on which I spent so many happy years.
"Holby has always been a hive of really exciting and imaginative stories and this won't be any different, it's going to be a cracker!"
Elliot will visit the hospital to see his old friend and protégé Jac Naylor, played by Rosie Marcel, but it soon becomes clear he also has an ulterior motive for his return.
Patricia will return in a special episode which goes beyond the realms of the hospital into different territory for Holby.
She added: "It's lovely to be returning to Holby. I really enjoyed my time there and made fantastic friends as well as meeting my husband.
"Returning after a decade is very weird but it's as friendly as ever and revisiting Diane feels like putting on an old glove.
"She had a tragic end and this storyline feels like it puts the character to bed with some peace and resolution. It's great."
Simon Harper, executive producer of Holby City and Casualty, is delighted both Paul and Patricia are reprising their roles.
He said: "How could we possibly celebrate Holby's 20th anniversary without a return stint from one of our most beloved characters?
"Elliot was the heart and soul of the hospital and the nearest thing to a father Jac has ever had - and her desire to please and prove herself to him at a particularly fraught time will have huge emotional consequences in our climactic story for 2019.
"I'm so delighted to welcome the glorious Paul Bradley back to his Holby family, and I also know just how hungry the audience have been for this moment, so it's wonderful to finally see it happen.
"It's not often we literally bring a character back from the dead, and no, Diane won't be walking out of the shower and telling her colleagues it was all a decade long dream.
"Her return is in itself an anniversary homage to a time on the show when we experimented quite regularly with genre and style, so the audience can expect something very different indeed in a unique and quirky episode where Ric faces a terrifying and life-changing choice, and the world of the hospital is literally turned upside down.
"I'm so pleased Patricia agreed to return in this most unusual way, Diane was a huge and popular character in Holby's first decade, and this will be such a treat for our long-term viewers."
What's more, the story of the Tan twins, the conjoined twin babies last seen on screen in 2008, will be revisited as the now-11-year-old patients return to the ward where their separation took place.
Holby City airs on Tuesday at 8pm on BBC One.
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