Twenty patients with stage D2 prostatic carcinoma were treated for up to 18 months with D-Trp-6-LH-RH. Results of more than 3 months of treatment on these 20 patients are reported. The analog was given SC once daily at a dose of 1,000 micrograms/day. All patients had bone pain and high levels of acid and alkaline phosphatase. After the first week of D-Trp-6-LH-RH administration, major decreases in bone pain and reversal of the signs of prostatism were observed. Acid phosphatase gradually fell, achieving normal values after 12 weeks. Initial plasma testosterone was within normal limits, but during treatment with D-Trp-6-LH-RH it fell to castration levels. Resting values of PRL, GH, TSH, and cortisol did not show significant changes. After TRH, TSH increased in five patients, but five did not respond. However, at 2 and 4 months, all patients released TSH in response to TRH. Two patients died during the treatment with D-Trp-6-LH-RH despite initial subjective responses and decreases in testosterone levels. The rise in acid phosphatase levels in these two patients was accompanied by a general deterioration, suggesting that they had androgen-independent cancer. One patient who developed progressive hepatic, bone, and pulmonary metastases in spite of previous orchiectomy was also treated with the analog. Three months later his acid phosphatase levels were within normal values, and partial regression of metastases was observed. These results demonstrate that D-Trp-6-LH-RH and other LH-RH agonists can be used as an effective endocrine therapy for advanced prostate carcinoma, thereby avoiding the side effects of estrogens or the psychological impact of surgical castration.