Renal tubular and vascular effects of 2 prostaglandin synthetase inhibitors, indomethacin and meclofenamate (2 mg/kg), were examined in anesthetized nondiuretic rats using clearance and micropuncture techniques. The 2 nonsteroidal anti-inflammatory drugs (NSAID) had similar renal effects. Indomethacin and meclofenamate inhibited renal prostaglandin synthesis by 69 and 90%, respectively. Urine flow, and Na and K excretion were reduced, 31-36%, by NSAID while they tended to increase in rats receiving vehicle alone. Glomerular filtration rate declined slightly in vehicle- and NSAID-treated rats, 10 and 12%, respectively, while renal blood flow and single nephron glomerular filtration rate were unaltered. The reductions in fractional Na, water and K excretion after NSAID were significantly different from the changes produced by vehicle alone, indicating enhanced tubular reabsorption after blockade of prostaglandin synthesis. NSAID did not alter inulin tubular fluid-to-plasma concentration ratios (TF/P)In) in paired tubular fluid samples re-collected from 26 late proximal puncture sites, indicating that net reabsorption along the proximal convoluted tubule was not affected by these compounds. The (TF/P)In ratios in samples re-collected from 24 distal tubules were also unaltered. The urine-to-plasma inulin concentration ratio increased from 287 .+-. 25 to 374 .+-. 36 (P < 0.001) after NSAID, indicating enhanced tubular reabsorption of water in nephron segments beyond the distal puncture site. NSAID may have increased tubular reabsorption in corticomedullary nephrons to a greater extent than in the punctured superficial nephrons. Intrarenal prostaglandins may attenuate net tubular reabsorption of water, Na, and K either in the distal nephron or, preferentially, in corticomedullary nephrons.