Administration of atriopeptin III (125, 250 and 500 ng/kg, intravenously) into pentobarbitone anaesthetized normotensive and DOCA-salt hypertensive rats had no effect on blood pressure or renal haemodynamics. Urine flow and absolute and fractional sodium excretion were increased by 48-90% from the lowest to the highest dose of atriopeptin III in the normotensive group, but were increased by over twice these amounts in the DOCA-salt hypertensive rats. Fractional lithium excretion and calculated proximal tubular fluid reabsorption were unaffected by the peptide in the normotensive rats, but in the hypertensive group atriopeptide III increased fractional lithium excretion by 25-50% and decreased proximal tubular reabsorption to a similar extent. Beyond the proximal tubule there were similar increases in fractional and absolute fluid handling in both groups of rats. These results demonstrated that in DOCA-salt hypertension there was increased sensitivity to the natriuretic activity of atriopeptin III which appeared to result from an increased responsiveness of the proximal tubule.