We examined the effect of verapamil treatment on cardiac protein kinase C (PKC) activity in streptozocin-induced diabetic rats. Basal cardiac PKC activity in diabetes increased in both cytosolic (by 94%, P less than 0.01) and membrane (by 41%, P less than 0.05) fractions as compared with that in controls. Subcutaneous administration of 8 mg/kg verapamil twice a day for 8 weeks induced a significant decrease in both cytosolic (by 59%, P less than 0.01) and membrane (by 50%, P less than 0.01) PKC activity in diabetes as compared with the activity in the non-treated diabetic groups. In contrast, cardiac cytosolic PKC activity in control rats was significantly (P less than 0.01) decreased by 41% as compared with that of the non-treated control group without there being any change in membrane PKC activity. Our data demonstrate that verapamil treatment may ameliorate the abnormal activation of cardiac PKC in diabetes.