The effectiveness of amantadine hydrochloride in prevention of illness and infection caused by Russian (H1N1) influenza was tested. The trial lasted seven weeks and was double-blind and placebo controlled. The dosage used was 200 mg daily. Efficacy in prevention of serologically confirmed clinical influenza was 70.7%. Efficacy in prevention of infection, symptomatic or asymptomatic, was 39.4%. Side effects seen were all mild, began within 2 days of the start of the trial, and terminated rapidly on cessation of prophylaxis. The withdrawal rate attributable to use of amantadine was 6.2%. Those who continued to receive prophylaxis for the remainder of the trial did not exhibit excess side effects. Amantadine is safe and effective in prophylaxis of H1N1 strains, as was shown previously for other subtypes of A influenza.