Norwalk virus infection is a common cause of gastroenteritis in humans. The clinical features and virologic and immunologic responses following oral administration of Norwalk virus to 50 volunteers were monitored. New ELISAs using recombinant virus particles as the antigen source were used to assess the pattern of virus shedding and the specific immune responses. Forty-one subjects (82%) became infected; 68% were symptomatic and 32% were asymptomatic. The proportion of subjects infected was similar for those with and without preexisting antibody (82% vs. 60%; P > .2). The magnitude of seroconversion was highest in subjects who had vomiting. The peak of viral shedding was between 25 and 72 h, and virus first appeared in stool at 15 h. Specimens collected 7 days after inoculation remained positive. These results show a higher infection rate, more subclinical infections, and longer virus excretion following Norwalk virus inoculation than previously recognized.