The indirect hemagglutination (IHA) test for coronavirus 229E antibodies was used for serodiagnostic and seroepidemiologic studies in a population of children. Subjects ranged in age from 5 to 19 years and lived in a home which participated in a longitudinal surveilance of respiratory illness (1960-1968). During this period 1477 respiratory illnesses were observed; 63 (4%) were associated with sero-response (fourfold or greater antibody rises) to 229E. An additional 105 sero-responses were associated with unreported or subclinical illness. The frequency of these infections was cyclical, and 229E and coronavirus OC 43 infections peaked in different years among the same population. Sero-responses occurred mainly in the fall, winter and spring quarters. Preexisting antibody was demonstrated in one-third of the children with 229E sero-responses. Clinical studies indicated that the most frequent complaints with 229E infections were sore throat, coryza and cough, and the most frequent findings were pharyngeal injection, coryza and fever.