Pituitary irradiation suppresses GH hypersecretion in patients with acromegaly. Within 10 yr after radiotherapy, up to 80% of patients achieve plasma GH levels below 5 micrograms/L. Whether this is sufficient to normalize plasma insulin-like growth factor I (IGF-I) levels, is unknown. We examined the effect of radiotherapy on plasma IGF-I concentrations in patients with acromegaly. We reviewed hospital charts of 140 patients with acromegaly seen in our institution between 1975 and 1996. Data on plasma GH and IGF-I were extracted and tabulated longitudinally together with the information about the concomitant medical therapy. We included data from the patients who received radiotherapy as a part of their treatment and whose IGF-I was monitored for more than 1 yr afterward. To avoid the potential bias, the data for patients who were referred to us for medical therapy, having failed radiation elsewhere, were excluded. A total of 38 datasets were submitted for the final analysis. The average follow-up was 6.8 +/- 0.8 yr (range, 1-19). Only 2 patients achieved age- and sex-adjusted normal IGF-I levels while off medical therapy. Noncured patients had a mean plasma GH level of 4.6 +/- 1.1 micrograms/L but still elevated plasma IGF-I levels (219 +/- 26% of the upper normal limit) at the last follow-up visit. A random GH concentration below 1.5 micrograms/L was associated with a pathologically high plasma IGF-I concentration in 43% of instances. Radiotherapy appears to be ineffective in normalizing plasma IGF-I levels in acromegaly. A multicenter study to reevaluate the future use of this modality in patients with acromegaly is warranted.