Antibody response to group A rotavirus (RV), investigated in paired sera from 72 infants and young children with acute gastroenteritis caused by an RV infection, was diagnosed on the basis of a fourfold or greater rise in group A common RV IgG antibody titer. Virus-specific IgM was detected in sera from 64 patients showing seroconversion; these were considered primary infection. RV was detected in stools of 56 (77.8%) patients with serologic evidence of infection and 54 were considered primary infection isolates: 39, serotype 1; 11, serotype 4; and 2, serotype 2. Two could not be typed. Neutralizing antibody studies showed that in primary infections serotype 1 induced an antibody response to serotype 4 at least fourfold lower than the homotypic response; serotype 2 elicited antibody titers to serotypes 1 and 4 at least fourfold lower than homotypic titer; and serotype 4 infections produced a response to serotype 1 as high as the homotypic response. Of 12 patients with primary infection, virus was not typed in 2 or detected in 10; however, the infecting serotype was identified on the basis of distinct patterns of homotypic and heterotypic antibody response.