Sprague-Dawley rats (31) undergoing a solute diuresis were subjected to 80 min infusions (125 .mu.mol/kg per min) of cationic AA [amino acid] (Lys, Arg), anionic AA (Glx, Asp) or neutral AA (Ala, Gly). Rats infused for 80 min with equimolar amounts of urea or dextrose served as controls (8). GFR [glomerular filtration rate] (Cioth) were measured 40 min before, during and 140 min after infusions. Albumin excretion rates were determined by radioimmunoassay. All AA infusates induced significant (P < 0.001) reductions in GFR compared to the control infusates (cationic AA, 62% .+-. 4, anionic AA, 57% .+-. 5, neutral AA, 33% .+-. 1 and controls, 8% .+-. 4) (.hivin.X .+-. SEM [standard error of the means]). Only cationic AA induced a significant increase in albumin excretion (360% .+-. 72; P < 0.001). AA-treated rats had histologic changes consistent with mild tubular injury compared to controls. AA had in common a nephrotoxic potential. This nephrotoxicity arose from the nonvariable portion of AA molecules since glycine, which had no variable (R) group, induced a significant reduction in GFR (32% .+-. 1). The ability of AA to decrease GFR was enhanced by certain R groups. R group charge was not a critical factor in producing this response. AA-induced increments in albumin excretion and reductions in GFR arose via independent mechanisms. Since AA infusions were commonly used in patients with ARF the possibility that such therapy might have a deleterious effect on renal function and on the subsequent recovery from ARF should be entertained.