Apple co-founder Steve Jobs has resigned as chief executive of the technology giant and will be replaced by chief operating officer Tim Cook.
Mr Jobs, who underwent a liver transplant following pancreatic cancer, said he could no longer meet his chief executive's duties and expectations.
The Silicon Valley legend will become chairman of the firm.
The 56-year-old has been on medical leave for an undisclosed condition since 17 January.
In a short letter to the board of Apple, Mr Jobs wrote: “I have always said if there ever came a day when I could no longer meet my duties and expectations as Apple's chief executive, I would be the first to let you know.
“Unfortunately, that day has come. I hereby resign as chief executive of Apple.
“I believe Apple's brightest and most innovative days are ahead of it. And I look forward to watching and contributing to its success in a new role.
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Consumers react to Steve Jobs' resignation
“I have made some of the best friends of my life at Apple, and I thank you all for the many years of being able to work alongside you.”
Apple board member Art Levinson paid tribute to Mr Jobs' contribution to the company: “Steve's extraordinary vision and leadership saved Apple and guided it to its position as the world's most innovative and valuable technology company.”
Apple shares have fallen 4.1% in the secondary listing in Frankfurt, having dropped more than 5% in after-market trading on New York's Nasdaq.
Analysts said the resignation was not unexpected, and would have little impact on the day-to-day running of the company.
“Steve is [still] going to be able to provide the input he would do as a chief executive,” said Colin Gillis at BGC Financial.
“But Tim has been de facto chief executive for some time and the company has been hugely successful. The vision and the roadmap is intact.”
This is a sad day for Apple and for the whole technology industry, as its most charismatic and successful leader of recent years brings down the curtain on an extraordinary career.
Steve Jobs addressed his brief letter of resignation not just to his company's board but to the Apple community – and millions worldwide will feel he was talking to them.
Forceful bosses whose personalities shape everything about their businesses are going out of fashion these days, for good reason many would say.
But Steve Jobs is a rare example of a chief executive who is synonymous with his company, a perfectionist who obsesses over every detail and has been the public face of just about every major product launch in the past decade.
It's difficult to imagine Apple without him – but he's leaving having revived what was an ailing business when he returned in the late 1990s, and turned it into the world's wealthiest company and one which has done more than any other in recent years to shape consumer technology.
Nor will customers see any real difference, analysts said.
“At the end of the day, consumers don't buy products from Apple because they're from Steve Jobs, they buy them because they meet their needs and they're good products, and they'll continue to do that,” Michael Gartenberg from Gartner told the BBC.
The company has some big products on the horizon such as the iPhone 5 and the iPad 3.
But while Apple shares slid, shares in two of Apple's main Asian rivals gained. Taiwan-based phone maker HTC rose 4.1%, while South Korea's Samsung Electronics gained 3.2%.
The firms compete with Apple in the smartphone and tablet-PC sector, and have been involved in legal battles with Apple over patent rights.
The boss of another rival in the phone market paid tribute to Mr Jobs' work.
“Steve Jobs is a visionary in the computing industry,” said Stephen Elop, chief executive of Nokia.
“We look forward to both Steve and his team having a positive impact on our industry for many years to come.”