During an outbreak of influenza A/Brazil/78 H1N1 infection, 47 volunteers with clinical and virological influenza of less than 2 days duration were treated in a randomized double-blind fashion for 5 days with 100 or 200 mg of amantadine daily or with 3.25 g of aspirin daily. The aspirin treatment group defervesced more rapidly (10.3 h versus 21.5 h and 23.6 h; P less than 0.01), but by the second daily follow-up visit, both groups of amantadine recipients exhibited greater symptomatic improvement. Bothersome side effects resulted in discontinuation of therapy by 35% of the aspirin treatment group but only 3% of the amantadine treatment group (P less than 0.05). Individuals who present to a physician during an influenza A epidemic with characteristic symptoms will experience symptomatic benefit from amantadine treatment, with negligible toxicity.