In January 1984, an outbreak of influenza caused by A/Victoria/7/83-like virus, a new H1N1 variant, occurred in an institution for mentally handicapped children and adults. During the first 18 days of the outbreak, 35 (81%) of 43 residents in two housing modules became ill, nearly all of whom had received influenza vaccine the previous autumn. Amantadine hydrochloride prophylaxis was initiated in two other housing modules and was continued for 28 days. While factors influencing the risk of introduction and secondary spread of influenza virus were comparable in all four modules, only ten (16%) of 63 residents who received amantadine were infected, only one of whom became symptomatic. Most side effects associated with amantadine were mild, but residents with active, preexisting major-motor seizure disorders demonstrated an increase in seizure activity compared with the previous eight-month period; those who took the maximum daily dose of amantadine hydrochloride (200 mg) and those who were also taking anticonvulsants other than phenobarbital were at highest risk.