Paula Radcliffe will not compete in the marathon at the London 2012 Olympics because of a foot injury.
The 38-year-old, who has never won an Olympic medal in four previous Games, was declared unfit after a test run this weekend.
Radcliffe said the thought of competing at London had kept her "fighting, motivated and focused".
In a statement, she added: "That is why it hurts so much to finally admit to myself that it isn't going to happen."
Radcliffe, who is still the women's marathon world record holder and a former world champion, has suffered with osteoarthritis in her foot during her career.
Radcliffe added: "However hard today is, finally closing the door on that [Olympic] dream, at least I can know that I truly have tried absolutely everything.
"Now however, is the time to accept that it is just not going to settle in time. As desperate as I was to be part of the amazing experience of the London Olympics, I don't want to be there below my best."
UK Athletics and the British Olympic Association said they will nominate Scotland's Freya Murray as the replacement for Radcliffe, to be approved under the Late Athlete Replacement policy.
UK Athletics head coach Charles van Commenee said: "This is obviously a disappointing day for Paula and our sport but it was important to her that if she made the start line it would be in the best possible shape.
"It wasn't meant to be and she has taken the right decision to withdraw at this stage.
"I think it is important that we don't look at Paula's career in Olympic cycles. She is undoubtedly one of the greatest female distance runners of all times and still holds the marathon world record.
"When we look back at her career it should be in the context of what she has achieved and not what she hasn't. I wish her all the very best for her recovery."
Radcliffe has been dogged by doubts about her fitness in the build-up to London 2012, leading to a trip to Germany for specialist treatment earlier in July.
She was as recently as last week.
Radcliffe has missed out on a medal in four Olympic Games appearances between 1996 and 2008, with her best performance coming on the track at the Sydney Games in 2000, when she was fourth in the 10,000m.
She won the marathon in the 2005 world championships in Helsinki and has won the London and New York marathons three times each.
The Bedford club runner broke the marathon world record in the 2003 London marathon in a time of two hours, 15 minutes and 25 seconds.