Oseltamivir is the prodrug of Ro64-0802 (GS4071), a potent and selective inhibitor of influenza A and B virus neuraminidases. Three randomized, double-blind, placebo-controlled, parallel-group studies evaluated oral oseltamivir for early treatment (75 or 150 mg twice daily for 5 days) or prevention (75 mg once or twice daily for 7 days) of experimental influenza B virus infection in healthy susceptible adults. Treatment study A (n=60) demonstrated similar trends to treatment study B (n=117), in which 75 mg doses of oseltamivir introduced 24 h after inoculation reduced median area under curve (AUC) virus titre (oseltamivir, 22.7; placebo, 131.1 log10 TCID50 x h/ml; P=0.002) and duration of viral shedding (oseltamivir, 23.9 h; placebo, 95.8 h; P=0.0005). In prevention study C (n=58), oseltamivir did not reduce infection rates (85 versus 84%) but significantly reduced median AUC virus titre (10.0 versus 66.9 log10 TCID50 x h/ml; P=0.03) and duration of viral shedding (36 versus 84 h; P=0.03) compared with placebo. Oseltamivir was well tolerated. No emergence of drug-resistant variants was detected by testing last-day isolates (n=112) in neuraminidase inhibition assays. These results indicate that oseltamivir has significant antiviral activity in experimental human influenza B virus infection when used for prophylaxis or early treatment.