1. With an average follow-up of 53 months (range 12-120 months), 19.4% (185/955) of men have had a cancer recurrence after radical prostatectomy for clinically localized prostate cancer. A detectable serum PSA was the only evidence of recurrence in 11.2%, whereas 2.2% have had a recurrence locally and 6% with distant metastases. 2. The actuarial status at 10 years was 70% for undetectable serum PSA; 23% for isolated serum PSA elevation only; 7% for distant metastases; and 4% for local recurrence. 3. In our study, no patient demonstrated disease progression (local or distant) without detectable serum PSA. 4. The actuarial likelihood of an elevated serum PSA increased with increasing clinical stage, Gleason score, preoperative serum PSA concentration, and pathologic stage. 5. The actuarial recurrence rate for tumors with a Gleason score of 7 was not statistically different from the recurrence rate for lesions of Gleason score 8-10. 6. There exist marked differences in actuarial recurrence-free probabilities for men with tumors of low Gleason score (< 7) compared with those with tumors of high Gleason score (> or = 7) when there is pathologically established capsular penetration. 7. Patients with preoperative serum PSA concentrations greater than 10.0 ng/mL are at a statistically increased risk of recurrence. 8. Men who have detectable serum PSA within the first year after surgery are at a significantly higher risk of disease progression than those men who have measurable serum PSA in postoperative years two and three. 9. Men with an isolated elevation of serum PSA after radical prostatectomy have a 25% likelihood of harboring an occult local recurrence. However, radiation therapy produces a sustained suppression of PSA to undetectable levels for 2 years or more in only 10% of men. This suggests that radiation therapy is not effective in sterilizing occult local residual tumor in many men. 10. Valuable information concerning disease recurrence and progression can be obtained through early postoperative measurement of serum PSA. This article demonstrates the long-term value of serum PSA as a measure of progression after anatomic radical prostatectomy.