The possibility of the host thymus-dependent functions in the development of insulin-dependent diabetes mellitus was investigated in athymic nude (nu/nu) mice and euthymic heterozygous (+/nu) littermates of CD-1 origin, injecting either the multiple subdiabetogenic doses of streptozotocin (STZ) or the D-variant of encephalomyocarditis (EMC-D) virus. A single high dose of STZ caused a rapid hyperglycemia in both +/nu and nu/nu male mice. However, multiple low doses of STZ (30 or 35 mg/kg b.w./d, for 5 days) induced delayed hyperglycemia only in +/nu male mice (>85%), and not in nu/nu male mice (<17%). It clearly shows inhibitory effect of the nude gene in induction of diabetes in CD-l mice by multiple low doses of STZ. The EMC-D virus produced hyperglycemia and insulitis in both +/nu and nu/nu male mice (76% diabetic and 73% diabetic, respectively). This shows that the immunological competence of the host may have no effect on diabetogenesis by EMC-D virus. Independent of their thymic function, female mice were quite resistant to the diabetogenic effect of the EMC-D virus. In EMC-D virus infected diabetic mice, the gross necrosis and insulitis were correlated only with the degree of hyperglycemia, regardless of the presence or absence of thymus. These results indicate that diabetes induction by EMC-D virus is not mediated by thymus (T-cell)-dependent processes.