A sustained-release formulation of a potent gonadotropin-releasing hormone (GnRH) agonist, Zoladex (D-Ser(But),6 Aza Gly10-GnRH; ICI 118,630; goserelin), was administered subcutaneously (3.6 mg/depot) to male rats once every 28 days for 2-24 wk to determine the extent to which pituitary-testis function could be suppressed and whether suppression was maintained throughout the period of treatment. Administration of Zoladex resulted in sustained decreases in weight of the testis, epididymis, seminal vesicles and prostate gland. The decreases were apparent within 2 wk of initiating treatment. Patchy degeneration of the seminiferous tubules and atrophy of the Leydig cells were observed, but did not progress beyond the degree observed after 1 month of treatment. Serum and testis testosterone were markedly depressed after 2 wk of treatment, as was testis [125I]hCG binding. Serum gonadotropins were also reduced by treatment. Serum androgen binding protein (ABP) was elevated, testis ABP content remained unchanged, and epididymal ABP content was reduced. The changes are consistent with the hypothesis that this compound affects both the anterior pituitary gland and the testis. These findings indicate that depot delivery systems are a convenient way to administer GnRH analogs for sustained treatment schedules.