Gleason grade, especially at low and high ends of the spectrum, is a known predictor of pathologic stage. What are needed are predictors of stage with Gleason sum 5 to 7 tumors, which encompasses the majority of clinically organ-confined tumors. In this study, we analyzed whether cell proliferation and apoptosis (programmed cell death) were correlated with stage in men with clinically organ-confined Gleason sum 6 to 7 cancer. We studied 98 radical prostatectomies with the following pathologic stages: organ-confined disease (n = 28); capsular penetration (n = 28); seminal vesicle invasion (n = 21); and pelvic lymph node metastases (n = 21). Histological sections from the radical prostatectomies were stained for cell proliferation using MIBI antibody (Ki-67) and for apoptosis using the TUNEL technique. The extent of staining was recorded as the number of positive cells per 1000 cells. Overall daily growth (kp) was calculated as: kp = (ki/2) - (apoptosis/0.5), based on the time of prostate cancer to undergo mitosis and apoptosis per day. Using logistic regression analysis, pathologic stage did not correlate with cell proliferation, apoptosis, or overall daily growth. These parameters also did not distinguish between Gleason sum 6 and Gleason sum 7 tumors. We supplemented these cases with examples of Gleason sum < or = 4 and Gleason sum > or = 8 to study cell proliferation and cell death in the full spectrum of Gleason grades. There was a significant difference (P = 0.005) in cell proliferation between Gleason sum > or = 6 and Gleason sum < or = 4 tumors, but apoptosis and daily growth were not significant. We conclude that cell proliferation and apoptosis do not correlate with pathological stage in clinically organ-confined cancer with Gleason sum 6 or 7, but that cell proliferation can distinguish between high (Gleason sum > or = 6) and low (Gleason sum < or = 4) grade tumors.