Serum VP7 (G) type- and isotype-specific anti-rotavirus antibodies were assessed among children monitored longitudinally over one or two rotavirus seasons in day care centers. Seventy-five pairs of blood specimens from 63 children were tested for anti-rotavirus antibodies. Stool specimens were collected weekly and tested for rotavirus antigen. G typing of detected rotaviruses showed that seven outbreaks of G1 and one of G3 occurred during the two seasons. G type-specific responses to the outbreak strain occurred among 79% of infected children and 9% of children with infection not detected (P < .001). Of children infected with G1, 54% had a heterotypic response; they were older (P = .048) and had higher preexisting G1 antibody levels than children who had only homotypic responses (P = .012). Higher IgA, IgG, and homotypic antibody levels to the antigenic site C of the G1 and G3 VP7s correlated with protection against infection and illness, homotypic antibody independently of IgA or IgG titers.