Epidemiologic evidence reveals striking racial differences in incidence and clinical behavior of prostate cancer among American men. In this study, we assessed the incidence of apoptosis and cell proliferation in prostate cancer specimens from African-American and Caucasian patients in an attempt to identify potential differences in tumor growth determinants between the two ethnic groups. METHODS. Apoptosis and cell proliferation were analyzed in archival paraffin-embedded prostatic tumors from 44 African-American and 35 Caucasian age-matched men who underwent radical prostatectomy for localized prostate cancer. Both groups had comparable preoperative prostate-specific antigen (PSA) levels, clinical stage, and Gleason scores, and neither group of patients received neoadjuvant therapy prior to surgery. Apoptotic status in prostate tumors was evaluated in situ, using the transferase deoxyuridine end labeling (TUNEL) assay, and the expression profile of two apoptotic proteins, bcl-2 and bax. The proliferative index was determined on the basis of Ki-67 antigen immunoreactivity. RESULTS. Apoptosis in malignant prostate cells was significantly higher in African American than Caucasian men (11.6% vs. 4.2%, P < 0.001). Interestingly, the rate of cell proliferation of prostate tumor cells was similar in the two ethnic groups (4.5% and 4.2%). The antiapoptotic protein bcl-2 was detected at significantly higher levels in tumors from Caucasian than African-American patients (40.8% vs. 31.6%, P < 0.05). Expression of bax, the apoptosis promoter, was consistently high among tumor epithelial cells in specimens from both racial groups (68%). CONCLUSIONS. These findings provide a novel insight into the molecular determinants of tumor growth that may underlie the ethnic differences in prostate cancer incidence and clinical behavior. Downregulation of bcl-2 expression may be potentially responsible for the loss of apoptotic control in prostate tumors from African-American men. This study may have significant clinical implications in the development of novel diagnostic approaches for biologically aggressive prostate cancer from diverse racial origin.