We examined sera from 42 patients 1 to 30 months of age for rotavirus immunoglobulin M (IgM), IgA, IgG, and IgG subclasses and sought to determine if serum antibody could serve as a reliable marker for prediction of disease severity. Infants in the first few months of life usually had high maternal IgG titers and, when they were infected with rotavirus, had low IgM titers or no IgM in acute-phase sera and poor seroconversions 3 weeks later, suggesting that maternal antibodies had inhibited viral replication and antibody responses. All patients >6 months of age had IgM in acute-phase sera, indicating that IgM is a good marker for acute rotavirus infection. IgG was the best overall predictor of an infection, as the convalescent-phase sera of 81% of the patients had a fourfold rise in the IgG titer. IgA titers in convalescent-phase sera and conversion rates were higher among patients >12 months of age than among children younger than 12 months. IgG1 was the predominant subclass detected in the acute-phase sera of some children and in all 28 convalescent-phase serum samples examined. Patients with preexisting acute-phase IgG titers of >100 or >200 had diarrhea that was less severe or of a shorter duration. These results indicate that serum IgG is the most reliable marker for seroconversion and is a consistent proxy for protection against severe disease.Previous studies have demonstrated that children infected with rotavirus develop systemic and local immune responses and are protected from severe disease upon reinfection (5, 6, 22, 38). However, our understanding of the true correlates of protection, essential for vaccine development, and the mechanisms of protection is still incomplete. At present, antibodies are generally considered a good marker for infection and a proxy for protection, but which antibodies (intestinal or serum, or both) are needed for protection remains unclear (25). While local immunity in the gut is believed to play a key role in protection, measurement of a local immune response in children is a challenge. Coproantibodies are subject to proteolytic degradation and are not considered a reliable marker for infection, and intestinal fluids are difficult to obtain from children, so we are left with measuring serum immunoglobulin A (IgA) titers as a proxy for local immunity (7,18,25,36). Because of differences among the reagents and assays used in different laboratories and the lack of detailed clinical information concerning individual patients in most studies (4,12,13,24,30,32,37), diverse opinions exist about the responses and roles of serum antibodies in children with acute rotavirus diarrhea.IgG is the most abundant Ig isotype and constitutes approximately 80% of the total Igs in human sera. The four IgG subclasses, IgG1 to IgG4, have different physiochemical, biological, and functional properties, such as the ability to activate complements (IgG1 and IgG3) and to cross the placenta and mediate opsonization of antigens by macrophages and neutrophils (IgG1, IgG3, and IgG4) (16). Measurement of...