NO2 + NO3 (NOx), the stable oxidation products of NO, and cGMP are widely accepted as indices of in vivo NO production. Whether acute changes in urinary excretion of nitrite + nitrate (UNOXV) can be taken to reflect acute changes in renal and/or systemic NO production is not known. The present studies were conducted in the conscious rat to investigate the effect on acute changes in UNOxV, of maneuvers that (a) enhance NO production and (b) act as diuretics. L-arginine (L-arg) and acetylcholine (Ach) produce equivalent NO dependent falls in renal vascular resistance (RVR), but a much greater increase in UNOX V is seen with L-arg. D-arg does not stimulate NO and has no renal vasodilatory effect, but produces a large rise in UNOX V, and SNP lowers BP but not RVR and results in a reduced UNOX V. None of the diuretics employed should stimulate the NO system or lower RVR; however, the proximally acting agents, acetazolamide and D-arg increased UNOx V, while the loop diuretic furosemide had little effect. H2O diuresis (a distal event) led to a fall in UNOx V. These data suggest that NOx is reabsorbed extensively in the proximal tubule and that inhibition of proximal reabsorption leads to an increase in UNOx V. Also, our results show that the relationship between UNOx V and UcGMP V is unpredictable. Therefore, we conclude that measurements of acute changes in UNOxV and/or UcGMP V should be interpreted cautiously, since they may reflect altered tubular handling of NOx rather than the acute activity of the systemic and/or renal NO systems.