Controversy exists concerning the effect of pre-existing renal disease on aminoglycoside nephrotoxicity. Since nephrotoxicity appears to be related to gentamycin concentration in the renal tissue, we studied the effect of renal mass reduction on renal tissue gentamycin concentration. Four groups of male Sprague-Dawley rats, who had undergone progressive renal mass reduction, were studied after injection with a single dose of gentamycin. As expected, serum gentamycin concentration was increased in nephrectomized animals and showed significant inverse correlation with the weight of the residual renal tissue. However, urinary gentamycin secretion rate was proportional with the weight of the residual renal tissue. Renal tissue gentamycin concentrations in the nephrectomized animals were significantly higher than that found in the sham-operated controls. The data indicate that renal tissue gentamycin concentration attained after a single dose of the drug is higher in the presence of reduced renal mass.