BACKGROUND: Neuraminidase inhibitors (NAIs) have been used since 2005 in France. OBJECTIVE: Influenza viruses isolated in hospital and community cases in winter 2005-2006 were evaluated for their sensitivity to NAIs. STUDY DESIGN: Isolates were tested in duplicate with a fluorescence-based neuraminidase assay. The IC(50) for oseltamivir or zanamivir was calculated for each strain. Mean IC(50) (+/-S.D.) are expressed in nM. Viruses with IC(50) superior or very superior to the upper limit (mean IC(50)+2.5 S.D.) were considered as outliers or resistant viruses, respectively. HA and NA genes for outliers, resistant strains and for a few sensitive strains were sequenced. RESULTS: Out of 225 B isolates, one was found resistant to both oseltamivir and zanamivir with a D197Y mutation in NA and eight isolates were outliers for oseltamivir and/or zanamivir. Out of 151 A (H1N1) isolates, one was found resistant to oseltamivir but sensitive to zanamivir with a H275Y mutation in NA, two isolates were resistant to zanamivir and three isolates were outliers for oseltamivir and/or zanamivir. New mutations were detected in outliers compared to sensitive viruses. CONCLUSION: Resistant influenza strains to NAIs are circulating at a stable and low level of 1% since the introduction of NAIs in clinical practice.