We reviewed our experience with salvage radical prostatectomy for locally recurrent cancer in 40 patients to assess the current complication rate and the results using prostate specific antigen (PSA) as an indicator of treatment outcome and to identify better criteria for the selection of appropriate candidates for this operation. Most recurrent cancers were detected by digital rectal examination (26 patients) or increasing serum PSA levels (10). The operation was technically challenging, with 6 rectal injuries (15%), 2 requiring temporary colostomy. Serious technical complications were more common (31%) among the 29 patients who underwent pelvic lymphadenectomy at the time of initial radiotherapy than among the 11 treated with external irradiation alone (9%). Urinary incontinence persisted in 18 of 31 evaluable patients (58%) and was successfully corrected with an artificial urinary sphincter in 9. A total of 21 patients (54%) had pathologically advanced disease (seminal vesicle invasion and/or lymph node metastases). Preoperative PSA levels but not clinical stage or biopsy grade correlated with pathological stage (p < 0.03). If the PSA was less than 10 ng./ml. only 15% of the patients had an advanced pathological stage, compared to 86% if the PSA was 10 or more. After 2 to 97 months (mean 39) 2 patients died of metastatic prostatic cancer, 5 had distant metastases and none had symptomatic local recurrence. At 5 years the actuarial nonprogression rate measured by PSA was 55 +/- 20%. The only pretreatment factor predictive of progression was the serum PSA level. If the PSA was less than 10 ng./ml. the actuarial rate of progression was significantly lower than if the PSA was greater than 10 (p < 0.05). The best results were in the subset of 18 patients with cancer confined to the prostate or immediate periprostatic tissue: 82% had no progression at 5 years. Within each of these pathological stages the results of salvage prostatectomy were similar to those for standard radical prostatectomy in patients with no prior irradiation. Although technically challenging, salvage prostatectomy provides excellent control of radio-recurrent cancer confined to the prostate or immediate periprostatic tissue and is best performed before the preoperative PSA level increases to greater than 10 to 20 ng./ml.