This study was designed to characterize the effect of L-arginine, a dibasic amino acid, on bicarbonate reabsorption (RHCO3) by the superficial proximal convoluted tubule using the technique of microperfusion in situ and on overall kidney RHCO3 using clearance techniques. Luminal perfusion of proximal tubules with L-arginine (5, 10, and 20 mM) resulted in a concentration-dependent inhibition of RHCO3. Capillary perfusion with L-arginine (10 mM) had no significant effect indicating that this amino acid must gain access into the cell from the luminal side to inhibit RHCO3. The inhibitory effect of L-arginine on RHCO3 was stereospecific since luminal perfusion with D-arginine (10 mM) had no significant effect on RHCO3. The lowest concentration of luminal L-arginine (5 mM) which produced a significant inhibitory effect on RHCO3 (about 13% inhibition) was comparable to that measured in the blood of rats infused with this amino acid (6.4 +/- 0.7 mM). Systemic infusion of L-arginine resulted in metabolic acidosis and only a slight increase in HCO3 excretion. To investigate whether the lack of overt bicarbonaturia was due to the reduced filtered load of HCO3 or to a stimulatory effect of acidemia on distal HCO3 reabsorption, blood bicarbonate was elevated by the infusion of NaHCO3. Under those conditions overall kidney absolute RHCO3, examined as a function of filtered load, was maximal in rats infused with L-arginine, thereby suggesting that when proximal HCO3 transport is inhibited, RHCO3 beyond the end of the proximal convoluted tubule increases in a load-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)