New strains of the flu virus are showing resistance to drugs that experts had hoped would slow the spread of any pandemic, research suggests.
Tamiflu is being stockpiled by the UK
Tamiflu is viewed as the best weapon currently available against a flu pandemic, and is being stockpiled by governments including the UK's.
But Japanese researchers found evidence of emerging resistance to Tamiflu, and a second drug Relenza.
The study is published in the Journal of the American Medical Association.
Experts have warned that a flu pandemic could claim millions of lives around the world.
There is concern that the H5N1 strain of the virus - known as bird flu - could mutate to gain the ability to spread easily from person to person.
At present the virus, a type of the A strain of flu, does not have this ability, although it has killed 170 people since 2003. These were mainly poultry workers, who came into very close contact with infected birds.
The Japanese researchers studied the effectiveness of Tamiflu and Relenza during an outbreak of a flu caused by a virus of the type B strain in the winter of 2004-2005.
Type B flu viruses usually cause smaller epidemics than type A.
Both Tamiflu and Relenza are used more extensively to treat flu in Japan than anywhere else in the world.
The researchers identified a variant strain of flu carried by one of 74 children treated with Tamiflu, which appeared to be less sensitive to the effects of the drug.
An analysis of 422 untreated patients found seven were carrying a strain of flu that was partly resistant to one or both of the drugs.
Some cases of resistance to Tamiflu in influenza type A cases - which typically strike at the beginning of the flu season - have already been found.
But until now little information has surfaced about type B influenza and its reactions.
Writing in the same journal, virology experts Dr Anne Moscona, of Cornell University, and Dr Jennifer McKimm-Breschkin, of Australia's Molecular and Health Technologies, warned the study had implications for public health policy.
They said the emergence of drug-resistant influenza B should draw attention to the importance of continual monitoring of flu strains, as well as the need for policies governing the use of antiviral drugs to be frequently reconsidered.
"Influenza viruses evolve rapidly and nimbly, which compels ongoing investigation of antiviral therapies that use alternative mechanisms of action and target different points in the viral life cycle," they wrote.