Some aspects of the toxicity of gossypol were investigated in ethanol-fed, gossypol-treated Sprague-Dawley rats, with and without protein malnutrition. Serum creatine phosphokinase activity was depressed in all gossypol-treated rats and gossypol caused greater decreases than ethanol in those animals that were fed the normal diet. Even though the adrenal glands were enlarged in all gossypol-treated rats, this was accompanied by depressed serum cortisol levels. Histopathological findings, including vacuolar degeneration of hepatocytes and dilation of the sinusoids in the liver, atrophy and leucocytic infiltration of cardiac myofibres, vacuolation of the renal glomerulus and cellular depletion of the spleen and thymus, were most severe in the protein-malnourished, gossypol-treated rats; these were generally absent in the other groups. These findings indicated that either adequate levels of protein in the diet and/or ethanol consumption have the effect of reducing gossypol toxicity, probably by reducing the amount of gossypol available for tissue exposure through enhanced metabolism and/or clearance from the body. However, an evaluation of the metabolic pathways involved in gossypol metabolism in ethanol-fed individuals might provide a better understanding of these observations.