The effects of oral administration of Carica papaya seeds extract on the morphology of pituitary, testes and sex accessory glands were studied. The C. papaya extract (50 and 200 mg/kg/day) was administered orally to sexually mature male Wistar rats for 1 and 8 weeks, respectively. The control group received corn oil (vehicle) only. The animals were killed after 1 and 8 weeks treatment for histological preparation. The microscopic examination of the sections of pituitary gonadotrophs (FSH and LH cells) treated with 200 mg/kg of C. papaya extract showed pronounced hypertrophy, while section of rats treated with 50 mg/kg showed mild hypertrophy and hyperplasia. Whereas the testes of rats treated with C. papaya extract at 50 and 200 mg/kg revealed gradual degeneration of germ cells, Sertoli cells and Leydig cells as well as germinal epithelium. However, tubules of epididymes of rats treated with extract, 200 mg/kg, appeared empty indicating the degeneration of sperm cells in the lumina. The sections of prostate glands of rats treated with 200 mg/kg extract showed coagulation of secretion in the lumina as well as empty tubules with cell debris, while the effect was reduced in rats treated with 50 mg/kg. The seminal vesicles showed progressive collapse and shrinkage of villi. These results suggest that C. papaya extract interfered with the pituitary – gonadal axis to influence male reproductive functions, which confirmed its antifertility property as reported previously. Copyright © 2005 John Wiley & Sons, Ltd.