Zanamivir, a potent, highly selective inhibitor of influenza virus A and B neuraminidase, has been evaluated in seven, similarly designed, placebo-controlled studies of the treatment of influenza. Patients with typical influenza symptoms were recruited when influenza was known to be circulating in the community. Six of these studies included a zanamivir 10 mg inhaled bd (for 5 days) treatment arm, the dose regimen submitted to regulatory agencies. Pooled analyses were conducted to evaluate efficacy more precisely in terms of the alleviation of symptoms in population subgroups and for secondary endpoints. Median time to alleviation of symptoms, the primary endpoint, was reduced from 6.0 days in the placebo group (n = 1102) to 5.0 days in the zanamivir group (n = 1133), P < 0.001. In febrile, laboratory-confirmed, influenza-positive (IP) patients, time to alleviation was reduced from 6.5 days to 5.0 days, a treatment benefit of 1.5 days (P < 0.001). A larger treatment benefit (3 days) was seen in IP patients who had severe symptoms at entry (n = 474, P < 0.001), compared with 1 day in patients whose symptoms were not severe (n = 1098, P < 0.001). Similarly, a 3 day treatment benefit (P = 0.003) was observed in IP patients aged n = 263), compared with 1 day (P < 0.001) in patients aged n = 305, P = 0.006). Pooled analyses of secondary endpoints showed statistically significant reductions in antibiotic use, time to return to normal activities and use of relief medication. In addition, reductions in symptom scores were apparent shortly after commencing zanamivir treatment. By the evening of the second day of treatment, the median total symptom score had fallen by 44% in zanamivir recipients compared with 33% in placebo recipients (P < 0.001). These results highlight the groups likely to show greatest benefit from zanamivir treatment, and confirm the clinical relevance of the treatment benefit.