Almost 3000 men who received a placebo in the Prostate Cancer Prevention Trial and who never had a prostate-specific antigen (PSA) level of more than 4.0 ng per milliliter during the seven years of the trial underwent a prostate biopsy at the end of the study. Biopsy revealed prostate cancer in 449 men (15 percent), 67 of whom had high-grade tumors. A PSA level of 4.0 ng per milliliter or less does not rule out the presence of prostate cancer, including high-grade tumors. When first described in 1979, prostate-specific antigen (PSA) was considered a useful marker for assessing treatment responses and follow-up among patients with prostate cancer. 1 After the publication of reports on several series in which the need for a biopsy of the prostate was based on the results of PSA tests, the potential of the PSA level as a screening tool was recognized. 2 , 3 Further experience led to the consensus that a PSA level of more than 4.0 ng per milliliter had predictive value for the diagnosis of prostate cancer. 4 Disease detection subsequently increased dramatically. 5 More recent data suggest that a . . .