The combined effects of cyclosporin (CYA) and prednisolone (PSL) on the function and morphology of pancreatic B cells of Wistar rats were investigated. Four 13-day treatment groups were compared; these were the O group (olive oil alone, p.o.), the P group (PSL 3 mg/kg/day, i.m.), the C group (CYA 20 mg/kg/day, p.o.), and the PC group (PSL 3 mg/kg/day, i.m. plus CYA 20 mg/kg/day, p.o.). Glucose tolerance was equally impaired in the C and PC groups. The pancreatic insulin content in the C group was 49.7% of that of the O group, whereas that in the PC group was 81.1%. Morphometric analysis using modified aldehyde-fuchsin staining revealed that 'percent beta-granule area' in the islet was 17.5%, 15.0%, 6.5%, and 7.8% in the O, P, C, and PC groups, respectively. Ultrastructurally, pancreatic B cells in the PC group showed CYA damage; however, a significant number of B cells exhibited hypertrophy of the rough endoplasmic reticulum and the Golgi apparatus, suggesting concomitant B cell hyperactivity in this group. These findings suggest that PSL does not aggravate the toxic effects of CYA on pancreatic B cells during short-term treatment; rather, it might be protective.