A new study has cast further doubt on the idea that a virus called XMRV causes chronic fatigue syndrome.
US scientists linked the condition, also known as ME, to a mouse-like virus in 2009 after finding it in blood samples.
Now, UK experts say the discovery was a "false positive", caused by cross contamination in the lab.
The illness may still be caused by a virus, they say, but not the one at the centre of recent controversy.
"Our conclusion is quite simple: XMRV is not the cause of chronic fatigue syndrome," said Professor Greg Towers, a Wellcome Trust senior research fellow at University College, London, who led the research.
"It is vital to understand that we are not saying chronic fatigue syndrome does not have a virus cause - we cannot answer that yet - but we know it is not this virus causing it."
XMRV (xenotropic murine leukemia virus-related virus) is a virus found in mouse DNA.
It was discovered in 2006, and was later found in samples from some patients with prostate cancer and chronic fatigue syndrome.
This lead to suggestions that the virus might be the cause of these conditions.
A paper providing some evidence in support of a link between chronic fatigue syndrome and the virus was published in the leading journal Science last year.
In the latest work, the team, from London and the University of Oxford, used DNA sequencing methods to study XMRV.
They say their evidence, published in the journal Retrovirology, shows the virus found in patient samples arose from laboratory contamination.
What is more, they think it is unlikely that the virus could actually infect people.
Professor Tim Peto, consultant in infectious diseases at the University of Oxford, said the original paper in Science came as a great surprise to experts.
"There have now been a number of attempts which have failed to find the retrovirus in other samples, and this research suggests that in fact XMRV is probably a contamination from mouse DNA," he said.
"These latest findings add to the evidence and it now seems really very, very unlikely that XMRV is linked to chronic fatigue syndrome."
But the authors of the original research say they stand by their conclusions.
"Nothing that has been published to date refutes our data," Dr Judy Mikovits, of the Whittemore Peterson Institute for Neuro-Immune Disease, said in a statement.
Dr Charles Shepherd, medical advisor for the ME Association, said patients should keep an open mind on the issue.
"The jury is still out," he said.