Zanamivir is licensed for influenza treatment, but may also play a role in prophylaxis either alone or in combination with vaccine in epidemic periods. We conducted a double blind placebo controlled trial to investigate the effect of zanamivir treatment on the humoral immune response to influenza vaccine. Forty young healthy volunteers were vaccinated with licensed trivalent influenza vaccine and received 20 mg zanamivir (24 subjects) or placebo (16 subjects) daily for a period of 14 days. No significant differences were observed in the magnitude or the time course of the antibody response to the influenza H3N2 and B strains between the two groups, in contrast the placebo group responded with higher antibody titres to the H1N1. Our results suggest that during an influenza epidemic, volunteers would only need to continue zanamivir treatment for the initial 12 days after vaccination whilst the vaccine induced protective antibody response developed.