Inbred lymphopenic, diabetes-prone (DP) and non-lymphopenic, diabetes-resistant (DR) BB rats in a specific pathogen-free (SPF) colony were subjected to a cross-intercross breeding experiment which showed diabetes to segregate as a recessive trait. All DP rats, but none of the DR and F1 rats, developed diabetes. In contrast, about 25% of the F2 rats developed diabetes which made it possible to study these rats without maternal influence of diabetes. All rats were bled at regular intervals between 30 and 150 days of age, and the samples analyzed for numbers of leukocytes, lymphocytes, neutrophils, monocytes and eosinophils. Leukocyte numbers tended to increase with age until about 100 days, and to decline thereafter. Males had more leukocytes than females. Coinciding with the time of onset of overt diabetes, there was a large increase in eosinophils, along with smaller increases in neutrophils, monocytes and lymphocytes. These data in SPF DP and DR BB rats and their cross-intercross offspring demonstrate that the overt onset of diabetes is associated with a significant leukocytosis.