The effect of the addition of N omega-nitro-L-arginine (L-NNA, 10 and 100 microM) to isolated rat kidneys perfused with a complex medium containing 21 amino acids has been studied. A cyclooxygenase inhibitor was added throughout to block prostaglandin synthesis. L-NNA caused significant reductions in renal perfusion flow rate (PFR, 9.8 +/- 1.4 vs. 15.9 +/- 1.1 ml.min-1.g kidney wt-1, P less than 0.0001), glomerular filtration rate (GFR, 566 +/- 57 vs. 705 +/- 47 microliters.min-1.g kidney wt-1, P less than 0.05) and an increase in the relative filtration fraction (%FF, 7.0 +/- 0.6 vs. 5.2 +/- 0.4%, P less than 0.05) compared to control kidneys. L-NNA perfused kidneys had a lower absolute sodium (72 +/- 9 vs. 88 +/- 4 mumol.min-1.g kidney wt-1, P less than 0.05) and glucose reabsorption (3.5 +/- 0.5 vs. 5.4 +/- 0.4 mumol.min-1.g kidney wt-1, P less than 0.05), corresponding mainly to a lower sodium and glucose filtration. However, the relative reabsorption of sodium and glucose in the presence of L-NNA was attenuated, too (82.8 +/- 2.0 vs. 87.0 +/- 3.3% P less than 0.05 and 91.3 +/- 1.1 vs. 94.1 +/- 0.5%, P less than 0.05). Potassium handling and protein excretion were not changed significantly; fractional protein excretion increased slightly with the addition of L-arginine (47 +/- 5 vs. 55 +/- 7 ng.microliters-1, P less than 0.05). The differences between control and L-NNA treated kidneys (with the exception of differences in FRGluc) could be fully (L-NNA, 10 microM) or partially (L-NNA 100 microns) reversed by adding L-arginine (1 mM) to the perfusion medium. The observed results could be obtained in two different rat strains (Sprague-Dawley and Wistar). Only L-NNA and L-arginine caused the observed changes, while D-NNA and D-arginine were without effect. It is concluded that NO/EDRF is basally released from the isolated perfused rat kidney, and is of importance not only in the regulation of renal hemodynamics but also in the regulation of renal tubular function.