The role of prostate-specific antigen (PSA) in the follow-up of patients after radiation therapy for prostate cancer is not well defined. There are no reports on long-term follow-up with PSA and serial PSA determinations, respectively. We followed 113 patients after radiotherapy for clinical stages A through D1 prostate cancer with multiple PSA measurements. External beam radiation has been applied to 98 patients and 15 received 125-iodine implantation. Eighty-eight of the 113 patients (78%) had a precipitously rising PSA with median doubling times of 14 (stage A), 15 (stage B), 7 (stage C), and 8 (Stage D1) months, respectively, at a mean follow-up of 5 years after radiotherapy. Twenty-three of the 113 patients (20%) appeared cured with a PSA of 1.7 ng/ml or less at a mean follow-up of 9 years. Two of the 113 patients (2%) continued to have a decreasing PSA 3 years after irradiation. Among the cured patients there was no relationship to clinical stage or histological grade. We conclude that about 20% of patients with clinical stages A-D1 prostate cancer can be cured by radiotherapy. They can be identified by a very low serum PSA level which seems to persist indefinitely. The remaining 80% who fail radiation therapy appear to have an accelerated growth rate suggesting tumor clonogen repopulation during radiotherapy.