Summary Studies of heterotypic antibody responses in volunteers infected or immunized with adenoviruses indicate the presence of 3 distinct immunologic groups of serotypes. These groups correspond to an earlier classification of adenoviruses by Rosen which was based on varying patterns of agglutination of rat and rhesus monkey erythrocytes. Review of published epidemiologic studies reveals a strong association of heterotypic antibody responses after natural illness with the classification described. Some interpretations of the role of this classification in the epidemiology of adenoviruses is offered and the possibility of a broadly effective vaccine prepared from serotypes representing the three immunologic groups is suggested.