Insulin action on kidney function was evaluated in 8 healthy subjects, (mean age 27 years) using the euglycaemic clamp technique. Insulin was infused at rates of 0, 20 and 40 mU·min-1·m-2 over consecutive periods of 120 min resulting in plasma insulin concentrations of 8±2, 29±7 and 66±14 mU/l. The renal clearance of 51Cr-EDTA, lithium, sodium and potassium was determined during the last 90 min of each period. Sodium clearance declined with increasing plasma insulin concentrations (1.3±0.4, 1.0±0.3 and 0.5±0.2 ml·min-1·1.73 m-2, p<0.001), while glomerular filtration rate (108±21, 104±21 and 108±20ml·min-1·1.73 m-2) and lithium clearance (a marker of fluid flow rate from the proximal tubules) 29±5, 29±4 and 30±4 ml·min-1·1.73 m-2) remained unchanged. Calculated proximal tubular reabsorption of sodium and water was unchanged, while calculated distal fractional sodium reabsorption increased (95.5±1.5, 96.4±1.2 and 98.1±0.7%, p<0.001). Potassium clearance and plasma potassium concentration declined, whereas plasma aldosterone and plasma renin concentrations were unchanged. In conclusion, elevation of plasma insulin concentration within the physiological range has a marked antinatriuretic action. This effect is located distally to the proximal renal tubules.