The aim of this study was to investigate the effects of chronic ethanol intake and cigarette smoke exposure on rat kidney. The animals were divided into four experimental groups: (1) the control group (C), (2) the ethanol group (E), (3) the cigarette smoke group (CS), and (4) the cigarette smoke plus ethanol group (CS+E). Apart from the control group, these were treated with ethanol and/or cigarette smoke for 6 months. The animals were killed and the kidneys removed to determine the levels of reduced glutathione (GSH) and malondialdehyde (MDA) and for histopathological analysis. The levels of GSH/g wet tissue were 1.58+/-0.09 micro mol, 0.91+/-0.05 micro mol, 1.14+/-0.06 micro mol, and 0.82+/-0.04 micro mol for C, E, CS, and CS+E, respectively. In groups of E, CS, and CS+E, the GSH values were significantly lower than that of group C animals ( P<0.05). Although, we detected lower GSH levels in the CS+E than the CS group ( P<0.05), a significant difference in GSH levels between CS+E and E was not observed. The levels of MDA/g wet tissue were 40.1+/-3.4 nmol, 71.4+/-2.8 nmol, 64.0+/-3.6 nmol, and 76.5+/-4.3 nmol, for C, E, CS and CS+E, respectively. In E, CS, and CS+E, the MDA values were significantly higher than in group C ( P<0.05). The increase in MDA levels in CS+E were not significantly different from groups E or CS. Histopathological analysis of the kidney slices showed severe degeneration of the tissues. Advanced hydropic degeneration of kidney tubules was clearly observed in the CS group. In group E, advanced tubular and interstitial damage, mononuclear cell infiltration and tubular thyroidization were clearly visible. In group CS+E, an intense inflammatory cell infiltration was detected under the transitional epithelium. We conclude that chronic exposure to ethanol and cigarette smoke may cause an oxidative burst in rat kidney by increasing the formation of reactive oxygen species.