The effects of the administration of the recently discovered immunosuppressant 15-Deoxyspergualin (DSP) on the development of insulin-dependent diabetes mellitus (IDDM) in diabetes-prone BB rats were studied. The data show that 2 mg/kg body weight DSP, administered six times a week from the 30th day up to the 105th day of age, significantly reduced the incidence of diabetes in diabetes-prone BB rats as compared with the PBS-injected controls. The drug was also able to reduce the signs of pancreatic insulitis and the percentages of W3/25+ and OX6+ splenocytes. Interruption of the treatment resulted in a later onset of diabetes in a high percentage of animals within 41 days. These findings suggest that 15-DSP may temporarily reverse the pathogenic mechanisms leading to beta cell destruction and autoimmune diabetes in a well-known experimental model of human insulin-dependent diabetes mellitus.