Two synthetic peptides, designated peptides 12G(A) and 12G(B), representing amino acids 174-188 of the G glycoprotein of respiratory syncytial virus (RSV) subgroup A (strain A2) and subgroup B (strain CH18537) were evaluated for their properties as subgroup-specific antigens for enzyme immunoassay (ELISA). These peptides were used to characterize the immune response of children with naturally occurring RSV infection during six annual epidemics in the Huntington area, West Virginia, USA; viz. 1978-1979, 1979-1980, 1980-1981, 1983-1984, 1989-1990, and 1990-1991. The study group comprised 43 paired sera from 42 infants and children, who ranged in age between 1 month and 5.5 years of age (median age 16 months). The inclusion criteria were subgroup identification of RSV, respiratory tract illness requiring admission to hospital, and the availability of paired sera. Five of 30 children with subgroup A and 3 of 13 children with subgroup B infections developed homologous or dual fourfold or greater antibody responses to peptides 12G(A) and 12G(B) during convalescence; six of these eight children also developed antibody rises to whole virus antigens. Twenty children (14 subgroup A and 6 subgroup B) developed such responses in antibody only to whole virus (not to the peptides), and 15 children (11 subgroup A and 4 subgroup B) failed to develop a rise in antibody. Children who developed rises in antibody to the peptides were usually less than 9 months of age, suggesting that a response to peptides was more likely to occur during primary infection. Peptides 12G(A) and 12G(B) of RSV G protein lacked sufficient sensitivity and specificity to serve as antigens for ELISA for characterizing the subgroup-specific immune responses to RSV infection in infants and children.