Patients from England, Austria, and Australia with recently diagnosed juvenile-onset insulin-dependent diabetes (type 1) mellitus (IDDM) and matched controls were tested for specific IgM responses to Coxsackie B1-5 viruses. 37 of 122 (30%) patients aged less than 15, but only 15 of 204 (6%) controls, were positive (p less than 0.005). Differences in Coxsackie B virus specific IgM responses between patients and controls were statistically significant for patients in England and Austria (p less than 0.005). Coxsackie B virus specific IgM responses were detected in only 3 of 31 patients aged greater than 16. Virus-specific IgM responses were directed against a single serotype, usually Coxsackie B4 or 5, in 23 of 37 (62.5%) children aged less than 15; 10 of 13 (77%) of children aged less than 7 had monotypic responses. Among families of Austrian patients with IDDM, 8 of 79 (10%) siblings had Coxsackie B virus specific IgM responses, 1 of whom subsequently had IDDM, but none of the 80 parents was positive. In contrast, there was no evidence of recent infection by mumps, rubella, or cytomegalovirus (CMV), since mumps-virus specific IgM was present in only 2 of 100 children with IDDM and 5 of 139 controls; no rubella or CMV specific IgM responses were detected in 60 sera from patients with IDDM.