1. Isolated rat kidneys were perfused at a constant perfusion pressure of 90 mmHg to study the natriuretic effects of atriopeptin III (AP-III) and to compare these effects with those of frusemide. AP-III (1 microgram) or frusemide (1 mg) were added to the perfusate (100 ml) after two 15 min control collection periods. 2. Compared with the control group, AP-III and frusemide increased urinary sodium excretion (UNa V, 5.6 +/- 1.1 and 4.6 +/- 0.6 vs control 1.8 +/- 0.3 mumol min-1 g-1, mean +/- SEM, P less than 0.01 and P less than 0.05, respectively), fractional sodium excretion (FENa, 4.8 +/- 1.1 and 6.7 +/- 0.8 vs control 2.0 +/- 0.2%, P less than 0.05 and P less than 0.001, respectively) and potassium excretion (UKV, 3.2 +/- 0.3 and 3.0 +/- 0.3 vs control 1.5 +/- 0.3 mumol min-1 g-1, both P less than 0.01). However, AP-III, but not frusemide, increased glomerular filtration rate (820 +/- 55 vs 590 +/- 24 microliter min-1 g-1, P less than 0.01) and urine flow rate (V 97.5 +/- 8.0 vs 44.1 +/- 5.2 microliter min-1 g-1, P less than 0.001). Calculated distal delivery of sodium (CNa +/- CH2O, 76.6 +/- 6.8 vs 30.7 +/- 3.8 microliter min-1 g-1, P less than 0.005) as well as fractional distal delivery of sodium [(CNa +/- CH2O)/CIn, 9.4 +/- 0.9 vs 5.1 +/- 0.6%, P less than 0.01] were increased by AP-III, but not frusemide.(ABSTRACT TRUNCATED AT 250 WORDS)