The M variant of encephalomyocarditis virus (EMC) infects pancreatic beta cells and causes the development of a diabetic syndrome in susceptible strains of mice. By examining four F1 crosses of susceptible and resistant strains of mice, we found that the development of diabetes after infection was inherited as a recessive trait. Analysis of the data from the F2 generation indicated that more than one gene was involved in the development of EMC-diabetes. The severity and frequency of abnormal glucose levels in EMC-infected animals was markedly influenced by environmental factors.