The effects of two unrelated diuretics, furosemide and amiloride on blood glucose, plasma insulin and glucose tolerance in the conscious rat are reported. Furosemide (1 mg/kg or 2 mg/kg) given intravenously caused an immediate but highly transient 23% and 53% fall in plasma insulin followed by a rise in blood glucose. The hyperglycaemic effect alone occurred in mild streptozotocin diabetic animals. Furosemide given with or 30 min before intravenous glucose (0.5 G/kg) caused glucose intolerance with diminished insulin response. None of these effects were observed in adrenalectomised animals. Amiloride (1, 5 or 10 mg/kg) given I.V. alone immediately increased plasma insulin (up to 213 U/ml) without affecting blood glucose. This effect was attenuated by mild streptozotocin diabetes. Amiloride given with or 30 min before glucose increased the insulin area without affecting glucose disappearance. Chronic administration enhanced glucose disappearance with increased plasma insulin response, and caused hyperkalaemia. Chronic furosemide administration had no effects. Possible mechanisms for these effects are discussed.