From 1975 to 1984, 120 patients were treated at Eastern Virginia Medical School with iodine-125 (I-125) interstitial implantation and pelvic lymphadenectomy as the definitive therapy for stage A2-C prostatic carcinoma. As might be expected, a higher incidence of local recurrence was seen with tumors at a more advanced stage but also with tumors of moderate and poor differentiation. Local tumor control in these groups did not compare favorably with patients externally irradiated during this period, of which 246 patients were available for study. Only 57% of recurrences with I-125 were clinically evident by 5 years follow-up with failures detected at up to 10 years, as opposed to the development of 91% of local recurrences by 5 years with external beam irradiation (P = 0.001), suggesting a later incidence of local recurrence with I-125 therapy. Major complications attributable to local tumor recurrence were also more frequent in implanted patients (20% vs. 8%; P = 0.006). The incidence of distant metastasis increased significantly in patients who experienced local recurrences, i.e., 83% versus 18%, with the expected adverse affect on survival. Disease-free survival by grade and stage showed a particular disadvantage for patients with moderately well and poorly differentiated tumors and stage C disease treated by I-125 therapy. In conclusion, then, it appears that I-125 interstitial implantation is well suited to only a select group of prostate cancer patients with well-differentiated, early stage disease and in most cases does not provide results comparable with external beam irradiation.