It has been hard to establish with certainty that radiation exposure is a risk factor for developing hyperparathyroidism. In part this is because many cases of hyperparathyroidism remain asymptomatic and escape clinical detection. We present results from a study of 2555 subjects who received external beam radiotherapy to the head and neck area for benign conditions before their 16th birthday between 1939 and 1962. The average length of follow-up was 36.6 yr. There were 36 confirmed cases of hyperparathyroidism. Based on a relative risk model, the excess relative risk increased significantly by 0.11/centigray; however, the confidence interval was wide (95% confidence interval, 0.0-17.2). The hyperparathyroidism rates and dose-response relationships were not affected by gender or age at first radiation treatment. The demonstration of a dose-response relationship within an irradiated cohort supports an association between radiation exposure and hyperparathyroidism and suggests that the calcium levels of individuals irradiated to the head and neck area should be monitored.