An outbreak of hand, foot, and mouth disease caused by coxsackievirus A16 occurred in Baltimore during the summer of 1968. Cases were identified in several sections of the city. The presenting complaints were sore mouth, anorexia, and rash. An exanthem, primarily on the hands and feet, was noted in 85% of the cases and all cases were associated with stomatitis. In 20 of 25 (75%) presumptive cases studied, the patients were shown to be infected with coxsackievirus A16, and 44% of asymptomatic family contacts also showed evidence of infection with the virus. Seventy-five percent of the patients with laboratory-confirmed cases were under the age of 5 years, and 53% of the positive family contacts were adults. That many adults and older children were found to be infected with coxsackievirus A16, probably indicates that the population had not been exposed to the virus before.