The frequency of diabetes mellitus was compared in non-obese diabetic mice before and after inadvertent exposure of the colony to mouse hepatitis virus infection. Prior to exposure, diabetes prevalence and cumulative diabetes incidence in 7-month-old mice was 65% and 25% in females and males, respectively. Diabetes incidence/quarter revealed a seasonal pattern with peaks in winter. After mouse hepatitis exposure, the diabetes incidence in the colony decreased and testing for mouse hepatitis antibody in blood samples revealed a persistent infection. In the offspring of mice delivered by caesarean section, the diabetic incidence increased sharply from a nadir of 36% to 95% and from 9% to 65% in females and males, respectively. In individual mice, diabetes resistance was strongly correlated to high titres of mouse hepatitis virus antibody. The results of this inadvertent viral infection demonstrate that a diabetes-susceptible genotype is strongly modulated by environmental factors. Investigators studying this diabetes model should strive for specific pathogen-free colony status and a high incidence of diabetes before attempting to investigate therapeutic modalities.