Gossypol acetic acid (GAA) displays anti-fertility and antioxidant behavior. The efficacies of different doses of gossypol acetic acid were investigated in male albino rats. Rats were allocated into four groups: control group and three GM-treated groups (2-4), that were injected with GM (5, 10, 20 mg/kg BW, respectively), through inrtaperitonial injection. Treatment of GAA was found to elicit a significant decrease in sperm counting, sperm motility, serum levels of testosterone, luteinizing hormone and follicle-stimulating hormone, whereas, the activities of testicular 17 beta-hydroxysteroid dehydrogenase and 17-ketosteroid reductase were increased. The activities of serum transaminases and alkaline phosphatase and hepatic glutathione peroxidase; glutathione reductase, superoxide dismutase and glutathione S-transferase and the level of hepatic glutathione were elevated. While, the lipid peroxidation end product; malondialdehyde, nitric oxide, and lipid profile and the activity of hepatic cytochrome P450 were decreased in GM-treated rats. The histological analysis of liver and testicular tissues showed sever hepatocyte damage in addition to abnormal localization of hepatocytic nuclei. Also, the testicular pathology of GM-treated rats showed depressed spermatogensis, sertoli cell toxicity and degeneration of seminiferous tubules. (C) 2010 Elsevier Ltd. All rights reserved.