A total of 347 patients with stages A2-C adenocarcinoma of the prostate treated with external beam radiotherapy and with pretreatment and 3-month prostate-specific antigen (PSA) levels were studied to evaluate the potential prognostic significance of the fall in PSA concentration from its baseline (PSAB) to its 3-month (PSA3) level. PSA levels fell in 333 patients (96%). With two exceptions, the patients whose PSA level did not fall had low PSAB and remained without evidence of disease. Since PSA levels fall virtually always, the fact that a fall occurs is of no prognostic value. When the magnitude of the fall relative to baseline was examined, patients with the largest falls had the worst outcomes. This paradoxical result was explained by the relationship between PSAB and PSA3. Regression analysis showed that the fall in PSA level was approximately proportional to the cube root of the baseline value. Thus, patients with high PSAB had high falls, but a high PSAB was an ovewhelming predictor for poor outcome. Hence, PSA fall relative to baseline was not a meaningful prognostic factor. The only factor of prognostic value was the absolute PSA3 value. Patients with PSA3 ≤2 ng/ml fared well at 4 years (freedom from relapse, 91%; incidence of rising PSA profile, 20%); patients with PSA3 > 2, but <-10 ng/ml had an intermediate, individually indeterminate outcome (freedom from relapse, 51%; incidence of rising PSA profile, 58%); patients with PSA3 >10 ng/ml can be said to have failed treatment (freedom from relapse, 50%; incidence of rising PSA profile, 90%). Although this analysis is based on short follow-up, it shows that the PSA value at 3 months after radiation provides a remarkably early assessment of response to treatment and the only patients who can be clearly stated to have responded well to treatment are those whose PSA level falls to ≤ 2 ng/ml. The long-term implications of 3-month PSA values await further follow-up.