We have investigated the effect of the D-Trp6 analogue of luteinizing hormone-releasing hormone (LH-RH), a superactive analogue of LH-RH, on the growth of two different models of prostate tumors in rats. Chronic administration of D-Trp6-LH-RH in a dose of 25 micrograms/day for 14-21 days significantly inhibited the growth of the chemically induced squamous cell carcinoma 11095 in Fisher 344 male rats. The weights of the ventral prostate and testes were also significantly reduced by treatment with this analogue. After 21 days of treatment, the animals no longer showed increases in serum luteinizing hormone and follicle-stimulating hormone levels in response to D-Trp6-LH-RH. Treatment of male Copenhagen F-1 rats bearing the Dunning 3327 prostate adenocarcinoma with 25 micrograms of D-Trp6-LH-RH per day for 42 days decreased the weights of both the ventral prostate and testes but had no effect on the weight of the anterior pituitary gland. The percentage increase in tumor volume was decreased to one-third and the actual tumor weight was decreased by 58% compared to untreated controls. The tumor doubling time was more than 4 times longer in rats receiving D-Trp6-LH-RH than in controls. Serum levels of luteinizing hormone and follicle-stimulating hormone were significantly decreased in rats receiving this analogue. In both Fisher 344 and Copenhagen F-1 rats, serum prolactin and testosterone levels were significantly decreased after treatment with D-Trp6-LH-RH, whereas progesterone levels were increased.