Despite the place of hypophysectomy as the primary treatment in acromegaly, external radiotherapy maintains a role as a relatively slow but effective therapy for inadequately treated patients or those unsuitable for operation. Over the last 25 years our radiotherapy regimen has differed from the published series in that we give a larger dose per fraction, with fewer treatments. We have analysed the efficacy and side-effects of this regimen in 27 subjects with acromegaly. Growth hormone levels have fallen by, on average, 27% per year in the first five years, 83% of subjects achieving a basal growth hormone of less than 10 mU/l. The acute and chronic side-effects of irradiation are discussed, including the relevance of estimates of biological potency, for example the Time Dose Fraction (TDF). One patient suffered visual loss that was most likely to be secondary to the radiotherapy. We also report the histological appearances of the pituitary fossa in five subjects previously treated with radiotherapy.