Effects of acute and repeated administration of cocaine and amphetamine on adrenal, gonadal and thyroid plasma hormone levels were studied in male rats. Acute and repeated cocaine (15 mg/kg i.p. one dose, or once an hour for 3 hr for 8 days) enhanced the corticosterone level at 45 min after administration. Amphetamine (5 mg/kg i.p. one dose, or twice daily for 14 days) elevated the level of corticosterone after 2 hr. Acute amphetamine increased the progesterone, testosterone and androstenedione plasma levels, whereas acute cocaine had no effect on those parameters. Repeated psycho-stimulants decreased the level of androgens. Neither acute nor repeated administration of psychostimulants had any significant effect on the level of the thyroid hormone T3. The T4 plasma level decreased following repeated amphetamine only. The above results indicate that repeated psychostimulants enhance the activity of the hypothalamo-pituitary-adrenal (HPA) axis and lead to a decrease in the hypothalamo-pituitary-gonadal (HPG) axis activity. On the other hand, the hypothalamo-pituitary-thyroid (HPT) axis seems to be more resistant to the psychostimulant action.