The long-acting synthetic somatostatin analog, SMA 201-995, was used to treat patients with advanced hormonal-refractory prostate cancer. Twenty-two of 24 study patients treated are evaluable for toxicity and 20 are evaluable for response. The dose of SMS 201-995 was 100 mg subcutaneously every 8 hours for 6 weeks. Two patients suffered intolerable gastrointestinal complications requiring early cessation of therapy. No patient had objective evidence of tumor regression. After developing a clinical suspicion that tumor growth accelerated with SMS 201-995, we observed 10 patients closely for 2 months before beginning SMS 201-995 treatment and for the first 2 months on the therapy. In these 10 patients, the serum prostatic acid phosphatase level rose at an accelerated rate after 1 to 2 months of treatment. Among the 20 patients treated and evaluable for response, new osseous metastases developed in 12 and new visceral metastases in 4; 1 developed disseminated intravascular coagulation and 2 developed neurologic complications (mean time to objective progression, 5.6 weeks). Six patients received salvage chemotherapy after disease progressed on SMS 201-995 therapy, 5 of whom have achieved objective tumor regressions. We believe SMS 201995 stimulates prostatic tumor growth and may sensitize tumor cells to subsequent chemotherapy.