Genetic and immunological markers in children with Type I diabetes have not been studied previously in Venezuela. We evaluated 91 newly diagnosed IDDM children mean age 7.8 +/- 4.5 (range 0.8-20.8 years), 51 females and 40 males. Eleven percent of first degree relatives had a family history of Type I IDDM; 56.7% had had upper respiratory infection prior to diagnosis and 12.7% had had either mumps or varicella. Peak incidence of disease was found in February and March and August to October. Eighty seven percent had HLA-DR3 and/or DR4 vs 36% of the Venezuelan general population; 81.6% were HLA-DQW2 and/or HLA-DQW8. We found 55.9% to have positive islet cell antibodies (ICA) with 4 of these having a positive complement fixation test. Three patients (7.9%) were found to have positive insulin autoantibodies. Only 3 out of 11 HLA-identical siblings had positive ICAs, while none had positive insulin autoantibodies. One of them also had a positive complement fixation test; this subject developed IDDM. No positive serotypes for enterovirus (Coxsackie-B) were found in our patients, but we detected 11 cases with elevated titers for cytomegalovirus antibodies and positive antibodies for measles, mumps, herpes and varicella were found in some children. These data confirm that most of our Type I diabetics carry HLA-DR3 or DR4 and that the heterozygous DR3/DR4 phenotype is markedly increased in this population; they also indicate that DR3QW2 and DR4QW8 are associated with increased risk in our population.