In order to elucidate the possible relationship between insulin autoantibodies (IAA), conventional (ICA-IgG) and complement-fixing (CF-ICA) islet cell antibodies and Coxsackie-B4 and mumps virus-specific antibodies (IgG, IgM and IgA classes), we studied 194 children and adolescents with newly diagnosed Type 1 (insulin-dependent) diabetes. Sixty-one (31.4%) of the subjects were IAA-positive at diagnosis and 73.8% (45/61) of these also had ICA-IgG compared to 51.1% (68/113, p less than 0.01) of IAA-negative children. CF-ICA showed no significant association with IAA. The levels of IAA were significantly higher in the patients with ICA-IgG compared to those without [5.9 +/- 1.6% (SEM) vs 2.5 +/- 0.3%, p less than 0.01]. The patients positive for IAA were younger at diagnosis than the IAA-negative ones; (7.1 +/- 0.5 vs 9.3 +/- 0.3 years, p less than 0.001) and this was also true for ICA-IgG-positive children (8.1 +/- 0.4 vs 9.4 +/- 0.5 years, p less than 0.05) in comparison to ICA-IgG-negative subjects. No significant associations were found between IAA or ICA on the one hand and a positive family history of Type 1 diabetes or metabolic derangements at diagnosis on the other. Subjects negative for ICA were more frequently positive for mumps virus specific IgG antibodies than the ICA-positive patients (50/80 vs 53/111, p less than 0.05), and Coxsackie-B4 virus-specific IgA antibodies were more common in the CF-ICA-negative than the CF-ICA-positive children (53/111 vs 29/80, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)