The activation of glycogen synthase after addition of glucose to isolated hepatocytes became impaired in BB rats after the development of insulin-dependent diabetes. This defect was associated with a decreased hepatic synthase phosphatase activity. Both features correspond closely to previous observations on alloxan-diabetic rats. In contrast, in hyperinsulinaemic db/db mice with a similarly increased plasma glucose concentration (non-insulin-dependent diabetes), the synthase phosphatase activity was essentially normal. We conclude that the decreased hepatic synthase phosphatase activity in insulin-dependent diabetes in rodents is due to the lack of insulin, rather than to the increased intrahepatic glucose concentration.