Carcinoma of the exocrine pancreas seems to be sex-hormone sensitive. Administration of agonistic analogs of luteinizing hormone--releasing hormone (LH-RH) creates a state of sex-hormone deficiency. Therapy with D-Trp-6-LH-RH was evaluated in 17 patients with unresectable and biopsy-proven adenocarcinoma of the pancreas (stage IV). Nine patients were male and 8 female, and the median age at diagnosis was 60 years. The majority of patients underwent a gastro-intestinal and biliary bypass. The therapy with D-Trp-6-LH-RH was started 3-31 days after bypass surgery. The analog was given at the dose of 1 mg/day subcutaneously for the first 7 days. Subsequently, the dose was reduced to 100 micrograms/day. One month after the start of the therapy the gonadotropin levels were in subnormal range. This therapy led to clinical improvement, better quality of life and an increase in survival time. The median survival time for all the groups was 7.2 months (men 7.4 months and women 6.9 months). LH-RH agonists appear to decrease pancreatic cancer growth by eliminating the stimulatory effect of sex steroids, and by direct effects on tumors. Further improvement in the clinical response in patients with inoperable pancreatic carcinoma might be possibly obtained by the combination of LH--RH agonists with modern somatostatin analogs.