Anti-influenza serum and nasal antibody titers were followed during a double-blind, placebocontrolled, randomized study assessing the prophylactic efficacy of 50, 100, and 200 mg/day of amantadine hydrochloride against experimental challenge with influenza A/Beth/1/85. The geometric mean titers (GMT) of serum hemagglutination inhibition antibody (P = 0.05) as well as serum influenza-specific IgG (P = 0.004) were significantly lower for all amantadine groups when compared to placebo. There were no significant differences in the GMT of either type of serum antibody titer comparing any of the three amantadine groups. Viral titers were also lower in the amantadine groups compared to the placebo group and not significantly different among the three amantadine groups. Nasal antibody titers in the 100-mg and 200-mg amantadine groups were significantly lower than placebo titers (P = 0.002). Nasal antibody titers in the 50-mg amantadine group did not differ significantly from titers in the placebo group (P = 0.892). Possible reasons for the differential effect of amantadine on the serum and nasal antibody response are discussed.