Sir Peter Williams, tipped as the next vice-chancellor of Oxford University, has announced after just 18 months that he is to leave his post as master of St Catherine's College.
The announcement has been described as a "blow" to those seeking to modernise Oxford.
Sir Peter, a successful industrialist and head of the university's modernising committee charged with improving Oxford's technological and scientific image, is the third college head to leave unexpectedly in four years.
In 1999, John Kay resigned as director of the Said Business School, frustrated by Oxford's bureaucracy.
A prominent member of the university described Sir Peter as the "bookies' favourite" to be the next vice-chancellor.
Sir Peter played down speculation. "I am leaving simply because I have a number of commitments which cannot be combined with the role of master," he said.
He said that speculation about the vice-chancellorship was misinformed.
He will leave his post as chair of Isis Innovation Ltd, the technology transfer arm of the university.
Many in the university speculated that tensions between colleges and the university were making the job of college head difficult.
"There are serious fault lines, with the management of joint appointments being one of the most serious," said one source.
Sir Peter said he was not leaving because of problems at the college. He will remain head of the university's modernising committee.
Sir Peter has a number of other commitments. He is chairman of the board of trustees of the National Museum of Science and Industry as well as president of the Institute of Physics. Next September he will become chair of the British Association for the Advancement of Science. Shortly after the announcement that he was to leave St Catherine's it was announced that he had joined the board of GKN plc.
He was chief executive of Oxford Instruments, the university's first spin-off company.
A senior fellow, commenting on behalf of St Catherine's, said that the college was sorry to be losing Sir Peter but "fully understood the pressures and commitment which have made his decision inevitable".
Oxford has 39 colleges. Between 1997 and 2001 there were 14 changes of head:
* 2001 - Colin Lucas retires as master of Balliol after seven years to continue as vice-chancellor; Elizabeth Llewellyn-Smith retires as principal of St Hilda's after 11 years; William Hayes retires as president of St John's after 14 years; Robert Stevens retires as master of Pembroke after eight years
* 2000 - Sir Keith Thomas retires as president of Corpus Christi after 12 years in post; Eric Anderson, rector of Lincoln College for six years, leaves to become provost of Eton; Sir David Smith retires as president of Wolfson after six years
* 1999 - Geoffrey Marshall retires as provost of the Queen's College after six years; Lord Plant, master of St Catherine's College for five years, leaves for Southampton University
* 1998 - Sir Stephen Tumim resigns as principal of St Edmund Hall after two years, following a vote of no confidence by the governing body; Sir David Rowland becomes president of Templeton College following the death of Michael von Clemm after two years in post
* 1997 - Lord Dahrendorf retires as warden of St Antony's College after ten years; Sir Crispin Tickell retires as warden of Green College after seven years; John Albery retires as master of University College after eight years.
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