Coxsackie B1-6 virus IgM responses were detected by an enzyme-linked immunosorbent assay (ELISA) in 11 of 28 (39%) children aged 3-14 years in whom insulin-dependent (juvenile onset; type I) diabetes mellitus (IDDM) developed in 1982. 5 patients had a homotypic response to Coxsackie B4 and 1 had a homotypic response to B5. A serum sample had been obtained from each patient 2 to 16 weeks after onset of IDDM symptoms. Islet-cell cytoplasmic antibodies (IgG) and complement fixing islet cell antibodies were detected in 15 of 18 sera tested, but only 6 of these sera were positive for Coxsackie-B-virus-specific IgM which suggests that Coxsackie-B-virus and islet-cell antibodies are not cross-reactive. Coxsackie-B-virus-specific IgM responses were present in only 16 of 290 (5.5%) age-matched non-diabetic London children whose sera were also collected during 1982. Sera from children with virologically confirmed Coxsackie-B-virus infections showed that development of homotypic or heterotypic Coxsackie B1-6 responses was age-related. 29 of 36 (81%) children aged 6 months to 4 years had a homotypic response, whereas 44 of 57 (77%) persons aged 15 years had heterotypic responses. Mothers of 2 children with Coxsackie-B-virus-induced neonatal myocarditis had Coxsackie-B-virus-specific IgM responses directed against serotypes 3 and 4, whereas their infants had a response to Coxsackie B2 virus alone.