Danazol is widely used in the management of endometriosis and mammary dysplasia. However, its mechanism of action is still obscure because of the few studies done and the controversial results obtained. Antigonadotropic activity has been postulated by some investigators, whereas others have observed no effect on the gonads. In the present study, three castrated female rhesus monkeys received 400 mg of danazol daily, by gavage for 19 days, while 2 controls received 400 mg of lactose daily. Blood samples were drawn every other day from 2 weeks prior to 3 weeks after the administration of the drug. Plasma luteinizing hormone (LH) and follicle stimulating hormone (FSH) decreased rapidly and then were maintained until danazol was discontinued. Prompt return to pretreatment levels occurred 1-2 days after the discontinuation of therapy. Prolactin levels were normal during therapy. Luteinizing hormone releasing factor (LH-RF), 100 microgram, administered intravenously during danazol therapy, caused a normal, prompt release of gonadotropins, demonstrating an intact pituitary response. The authors conclude that 1) danazol is a potent antigonadotropic agent, 2) its effect is abolished promptly after discontinuation, and 3) its probable biological action is at the hypothalamic level.