A controlled investigation of chemoprophylaxis with amantadine hydrochloride during an epidemic of influenza A was performed in nonimmune students. Illness was significantly decreased and serologic evidence of infection reduced by treatment. During the post-treatment period, while influenza was still prevalent, an accelerated rate of infection occurred among persons previously protected by chemotherapy. When used, chemoprophylaxis should be continued until influenza is no longer prevalent or, preferably, should be combined with vaccine administration to ensure protection after treatment.