A series of 115 previously untreated patients displaying clinical stage C prostatic carcinoma with no evidence of distant metastases received combination therapy using the antiandrogen flutamide and the LHRH agonist [D-Trp6, des-Gly-NH(2)10]LHRH ethylamide; the average follow-up was 3.9 years. Twenty-eight patients showed treatment failure with a probability of disease-free survival of 91.2% at 2 years. Twenty patients died from prostate cancer and 10 from other causes, the survival probability being 93.4% at 2 years. Local control was achieved rapidly in all patients. Urinary obstruction and hydronephrosis were corrected in all cases. When compared with data obtained after single endocrine therapy (orchiectomy or oestrogens) or radiotherapy, the treatment failure rate at 2 years was more than 3.0-fold lower after combination therapy (8.8%) than monotherapy (28.4%). The death rate 2 years after the start of combination therapy was 6.6% and was on average 22.2% (3.6-fold higher) in the studies using monotherapy (orchiectomy or oestrogens) or radiotherapy. The present data suggest that treatment of prostate cancer with combination therapy before clinical evidence of dissemination of disease permits more efficient control of local disease and a decreased rate of progression to metastatic disease.