To assess the value of serum prostate-specific antigen (PSA) in prostate cancer follow-up, we prospectively studied 107 consecutive patients with: (1) pathologically confirmed prostate cancer; (2) definitive prostatectomy and/or radiation therapy greater than or equal to 3 mo prior to bone scanning; and (3) one bone scan and serum PSA sampling within 3 mo of each other. The mean and range of patient follow-up since definitive therapy was 1.6 and 0.5-8 yr, respectively. Abnormal bone scans were correlated with pertinent radiographs. Of 107 bone scans, 16 demonstrated metastatic bone disease. A PSA value of less than or equal to 8 ng/ml excluded bone metastases with a predictive value of a negative test of 98.5%. Without radiographic correlation, abnormal bone scans rarely represented metastases if the PSA value was less than or equal to 8 ng/ml. In summary, serum PSA concentration determines the need for follow-up bone scanning and assists in scan interpretation in patients status post definitive therapy for prostate cancer.