The potential prognostic significance of prostate-specific antigen (PSA) serum concentrations was evaluated in 171 patients with stages A2 to C adenocarcinoma of the prostate treated with external beam radiotherapy. After a median follow-up of 17 months, 12 patients sustained relapse of disease and PSA levels were found to be prognostically significant in three ways. (a) Pretreatment PSA level: none of 59 patients with a pretreatment PSA level less than or equal to 4 ng/ml relapsed to date and only one developed a subsequently rising PSA profile; 7 of 102 patients (7%) with a pretreatment PSA level in the range 4-40 ng/ml relapsed and 17 (17%) showed a rising PSA profile; 5 of 10 patients (50%) with a pretreatment PSA level greater than or equal to 40 ng/ml relapsed and six (60%) developed rising PSA values. The differences were significant and were maintained when patients were stratified by stage or grade. (b) PSA level at 6 months: for patients with pretreatment PSA levels in the range 4-40 ng/ml, a 6-month value greater than 2 ng/ml predicted a significantly worse outcome than a 6-month value less than 2 ng/ml. (c) Rising post-treatment PSA values: following a radiation-related nadir in PSA levels, 24 patients experienced rising PSA values and 8 (33%) relapsed at a median time of 5 months after onset of the rising values--a significantly higher relapse rate than observed in patients with non-rising PSA values. Whether the majority, or all, of the patients with rising PSA levels relapse, requires further follow-up. In conclusion, serum PSA levels are strong prognostic determinants of outcome following radiotherapy for prostate cancer and appear to add prognostic information independently of tumor stage and grade.