Conventional megavoltage irradiation of GH-secreting tumors has predictable effects on tumor mass, GH, and pituitary function. 1. Further growth of the tumor is prevented in more than 99% of patients, with only a fraction of a percent of patients requiring subsequent surgery for tumor mass effects. 2. GH falls predictably with time. By 2 years GH falls by about 50% from the baseline level, and by 5 years by about 75% from the baseline level. The initial GH elevation and the size and erosive features of the sella turcica do not affect the percent decrease in GH from the baseline elevation. 3. With prolonged follow-up, further decrease in GH is seen at 10 and 15 years, with the fraction of surviving patients achieving GH levels less than 5 ng/mL approaching 90% after 15 years in our experience. Gender, previous surgery, and hyperprolactinemia do not seem to affect the response to treatment. Patients with initial GH greater than 100 ng/mL are significantly less likely to achieve GH values less than 5 ng/mL during long-term follow-up. 4. Hypopituitarism is a predictable outcome of treatment, is delayed, and may be more likely in patients who have had surgery prior to irradiation. There is no evidence that this complication is more common in patients with acromegaly than in patients with other pituitary adenomas receiving similar treatment. 5. Vision loss due to megavoltage irradiation--using modern techniques and limiting the total dose to 4680 rad given in 25 fractions over 35 days, with individual fractions not exceeding 180 rad--is extremely rare. The reported cases have occurred almost entirely in patients who have received larger doses or higher fractional doses. The theory that patients with acromegaly are prone to radiation-induced injury to the CNS and optic nerves and chiasm because of small vessel disease is not supported by a review of the reported cases. 6. Brain necrosis and secondary neoplasms induced by irradiation are extremely rare. 7. Although anecdotal evidence raises the question of changes in intellectual function following irradiation, this has not been studied in adults receiving pituitary irradiation.