Combination chemotherapy with Adriamycin and cyclophosphamide was administered to 22 men with progressive tumor following hormonal treatment for metastatic carcinoma of the prostate. Objective partial response was documented in 7 patients (32%); an additional four (18%) had stable disease for a minimum of four months, and 11 (50%) were non-responders. Patients with partial response had a median survival of 14 months and lived significantly longer than those with no response (median five months); survival of men with stable disease approximated that of partial responders. Serial utilization of multiple staging procedures during chemotherapy demonstrated that although no single test allowed identification of all patients with objective tumor response or progression, improvement in median of five parameters could be documented in responding patients. In patients adequately studied at the time of disease progression, deterioration in a median of six tests was found. Serum acid phosphatase radionuclide bone scan, and plasma carcinoembryonic antigen were the most sensitive procedures which detected both objective tumor response and progression. Toxicity of chemotherapy was acceptable except in patients with prior radiation therapy. Administration of Adriamycin and cyclophosphamide was associated with clinical benefit in half of our patients with hormone-resistant prostatic cancer. Tumor response and progression can best be objectively assessed if several staging procedures are serially employed during treatment.