A total of 161 patients diagnosed as having stage B (134 patients) or C (27 patients) prostate cancer were randomly assigned to radical prostatectomy alone or to 3 months of neoadjuvant combination therapy with the anti-androgen flutamide and an LHRH agonist before radical prostatectomy. Neoadjuvant combination therapy before radical prostatectomy decreased cancer positive surgical margins from 33.8% in the control group to only 7.8%, thus leaving 92.2% of patients with negative margins at surgery for a 39.2% increase in specimen confined disease. Although on average the final stage determined at histopathological examination of the surgical specimen was more advanced than predicted at initial diagnosis in 33.8% of control patients, an opposite observation was made in the group of men who received the 3 month neoadjuvant combination therapy where the final stage, instead of being more advanced, was less advanced than at diagnosis in an average of 21.1% of men for a net 54.9% improvement of staging in favour of combination therapy. On the other hand, organ confined disease increased from 49.3% to 77.8% of patients after 3 months of combination therapy, for a 57.9% increase in the incidence of organ confined disease. Although long term follow up of these patients is required to determine the impact on survival, the marked influence of neoadjuvant combination therapy on the stage of the disease suggests the possibility of a major improvement in the morbidity and mortality from prostate cancer.