The effect of treatment of rats with gentamicin (80 mg/kg/day for 6 days), oral doses of spironolacatone (20 mg/kg/day for 6 days), and the combined treatment (spironolactone + gentamicin) on renal histology and reduced glutathione (GSH) concentration, and some serum constituents indicative of kidney function were studied. The serum concentrations of creatinine and urea were not significantly affected by spironolactone treatment, but were significantly elevated (P<0.05) by gentamicin administration. The antibiotic treatment also reduced GSH concentration and caused a moderate renal cortical necrosis. However, rats exposed to spironolactone + gentamicin revealed drastic increases in the serum urea and creatinine concentrations amounting to about 1.8 and 2.1 times those of rats treated with gentamicin alone, respectively. The histological examination of slides of the renal cortex of rats exposed to the combined drugs exhibited more extensive necrosis in the tubules when compared to those treated with gentamicin alone. The reduction in GSH induced by gentamicin was unaffected by the concomitant treatment of gentamicin and spironolactone. The concentration of gentamicin accumulated in the renal cortex was significantly larger (twofold) in rats treated concomitantly with spironolactone + gentamicin than in rats treated with gentamicin alone. The present results indicate that spironolactone aggravates gentamicin-induced nephrotoxicity in the rat.