Glucose homeostasis in normal rats was studied after chronic or acute administration of quinine. Male rats received a daily dose of 10-30 mg/kg of quinine in the drinking water for 20 weeks. The high dose caused a slight decrease in food intake and weight gain. Though basal plasma insulin levels were increased in treated rats, their plasma glucose levels were only slightly and not consistently decreased. After oral or intravenous administration of glucose, the plasma insulin levels were higher and the disappearance rate of glucose was greater in rats receiving quinine than in the controls. The insulin content of the pancreas was not affected by quinine treatment. Intraperitoneal injection of a high dose of quinine (30 mg/kg) transiently increased plasma glucose and insulin levels. The insulin response was increased during a subsequent administration of glucose but the glucose levels were not modified. This study shows that chronic administration of quinine increases plasma insulin levels, accelerates disposal of oral or intravenous glucose but does not cause hypoglycaemia in normal rats.