Coronary artery disease occurred in four young men (mean age 41 years) who had received curative irradiation therapy for mediastinal malignancies 12 to 18 (mean 15) years previously. None was at high risk for developing coronary artery disease by Framingham criteria. Angiography demonstrated proximal coronary artery disease with normal distal vessels. Distribution of the lesions correlated with radiation dosimetry in that vessels exposed to higher radiation intensity were more frequently diseased. Three patients had coronary bypass grafting for intractable angina and are asymptomatic at 10 to 43 months. A total of 163 patients underwent mediastinal irradiation for lymphoma or thymoma between 1959 and 1980. Among the 29 who survived 10 or more years, five (18%) developed severe coronary artery disease, implicating thoracic radiotherapy as an important risk factor. Because of the importance of mantle irradiation in the treatment of lymphomas, the prevalence of these neoplasms, and the survival patterns following treatment, many long-term survivors may be at increased risk for the development of coronary artery disease. Recognition of the relationship between radiotherapy and coronary artery disease may lead to earlier diagnosis and more timely intervention. Standard surgical treatment may be particularly beneficial because of the relative youth of most of these patients and because the proximal distribution of typical lesions increases the likelihood of complete revascularization.