Norwalk virus infection was sought in 48 US, 49 Puerto Rican, and 27 Mexican adults attending medical school in Guadalajara (Mexico) who were enrolled in a 2-year longitudinal study. Serum specimens were collected quarterly and as acute- and convalescent-phase samples around episodes of gastroenteritis. The reciprocal Norwalk virus geometric mean titer (GMT) for Puerto Rican students (567) was significantly higher than that of the US students overall (294; P less than .001) and for four of nine quarterly periods. The reciprocal Norwalk GMT for Mexican students (748) was also significantly higher than that of the US students overall (P less than .001) and for seven of nine quarterly periods. The average percentage of students per year with seroconversions was 30%. The rate of Norwalk virus infection averaged 0.36 episodes per student-year. Symptoms of gastroenteritis associated with seroconversion occurred in 45% of students. Preexisting serum antibody did not protect against subsequent Norwalk virus infection in these subjects. All student groups had similar rates of infection and symptomatic gastroenteritis.