The present immunohistochemical study of radiation-induced damage in major blood vessels is based on a multidisciplinary study (Schultz-Hector et al., Radiother. Oncol., 38: 205-214, 1996) investigating the combined effect of IORT of the coeliac axis and upper abdominal ERT. The paper describes the sequential changes occurring in the coeliac artery after IORT with 30 Gy, i.e. during and after combined IORT and fractionated ERT (total dose 40 Gy). Within 24 h after IORT, the arterial wall was found to be invaded by TNF-alpha positive macrophages, which later on disappeared within 7-14 days. At 2 days post-IORT, the medical smooth muscle cells were strongly positive for TNF-alpha and remained positive throughout the observation period of 63 days. At 80 days, a comparison of different IORT dose groups showed that TNF-alpha expression after 20 and 30 Gy IORT plus 40 Gy ERT had subsided, while it was still strongly evident after 40 Gy IORT. Negative reactions in sham irradiated animals or animals treated with ERT alone indicate that TNF-alpha expression was caused by IORT. After > 30 days post-IORT, there was increased collagen type I deposition in the adventitia. In two animals receiving the full ERT course, intimal proliferations involving mainly smooth muscle cells were observed. Our findings indicate that some features typical of radiation induced arteriosclerosis such as periarterial fibrosis and intimal proliferations can occur as early as < 60 days postirradiation. Macrophage invasion as well as TNF-alpha expression in medial smooth muscle cells are known to be important steps in the development of spontaneous atherosclerotic lesions. Therefore, early TNF-alpha induction in the arterial wall by a high local dose of X-irradiation may be regarded as one initiating factor of chronic radiation-induced arteriosclerosis.