Forty-five university students with proved influenza A/USSR/77 H1N1 infection were randomly treated with either amantadine hydrochloride (14 students), rimantadine hydrochloride (19 students), or placebo (12 students). By 48 hours after initiation of therapy, amantadine and rimantadine recipients had significantly less fever and greater improvement compared with subjects given the placebo. Minor reversible CNS side effects at the end of the five-day course of therapy were observed in one third of the amantadine-treated subjects. However, both amantadine and rimantadine recipients returned to classes earlier and shed smaller amounts of virus than placebo recipients. Thus, both drugs exerted a notable therapeutic effect. Hence, during an influenza outbreak, five days of empirical therapy with amantadine or rimantadine for persons with an influenza-like syndrome should ameliorate clinical symptoms and might decrease spread of virus.