The incidence of clinically organ-confined prostate cancer has markedly improved in programs designed to detect this disease by utilizing a combination of diagnostic modalities including digital rectal examination (DRE), transrectal ultrasonography (TRUS), and prostate-specific antigen (PSA). Biopsies were performed on 436 men who had abnormal findings on DRE, TRUS, or PSA. Overall, 39 percent of these men had histologic confirmation of prostate cancer. TRUS diagnosed more cancer (94%) than either DRE (80%) or PSA (89%), while the combination of TRUS and PSA diagnosed a similar number of cancers as the combination of DRE and PSA (100% vs 98%). The positive predictive value (PPV) of DRE and PSA combination was significantly better than that of TRUS and PSA (p = 0.01), but was not different from that of a combination of all three tests. DRE and PSA would have missed 4 cancers, but would have cost approximately 140 percent less than any program employing TRUS. Consequently, we recommend that the combination of DRE and PSA be used in primary early detection for prostate cancer and that TRUS be performed only when either or both DRE and PSA results are abnormal.