Seventeen patients with histologically proven adenocarcinoma of the prostate were selected for evaluation of their immunologic competence and therapy with bacillus Calmette-Guérin (BCG). All patients were in stage D. The immune response was explored in two main aspects: cell-mediated and humoral immunity. Delayed skin hypersensitivity reaction with purified protein derivative (PPD), streptokinase-streptodornase (varidase), Candida, mumps antigen, and Trichophyton were tested. Lymphocyte reactivity was measured by in vitro blastogenesis. Serum immunoglobulin levels and serum protein electrophoresis were also measured. The patients were then divided in two groups according to the skin test response to PPD. Group 1 (PPD-positive) consisted of seven patients. Group 2 (PPD-negative) consisted of ten patients. In group 1, two patients were treated with intraprostatic injection of BCG every week in the following doses: 1 cc the first week, 2 cc the second week, 4 cc the third week, and 6 cc the fourth week. The five remaining patients in this group received only 1 cc every week for 4 weeks. The group 2 patients (PPD-negative) were stimulated by oral intake of BCG in an attempt to convert their skin tests to positive. All patients revealed varying degrees of immunodepression. None of the patients in group 2 (stimulated by oral intake of BCG) converted to positive skin tests. Three patients in group 1 treated with BCG showed necrosis of the tumor. The different aspects of immunodepression in this disease are analyzed and correlated to the clinical staging, histologic grading, and response to therapy. The mechanism of BCG action in advanced prostatic carcinoma is discussed.