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In order to gain further understanding of the late effects of radiotherapy on oral mucosa, we analysed the histomorphological alterations, the cell populations in the subepithelial tissue, and the endothelial expression pattern of different adhesion molecules. Biopsies were taken from patients before irradiation, directly after 60 Gy, and 6–12 months after radiotherapy. Besides the histomorphological evaluation of the vessels, the endothelial expression of ICAM-1, VCAM-1 and E-selectin was determined as well as the distribution of LFA-1-, Mac-1-, VLA-4-, RM3/1-, 27E10- and 25F9-bearing cells in the subepithelial tissue. The expression of ICAM-1 was downregulated after radiotherapy, whereas the percentage of LFA-1- and VLA-4-bearing cells increased. VCAM-1 remained at low levels. The subepithelial infiltration was still dominated by RM3/1-positive macrophages. The number of vessels decreased, while the lumen of the remaining vessels increased. In conclusion, the late effects of radiotherapy are characterized by a decreased number of blood vessels and by significantly different expression patterns of the adhesion molecules studied, and of integrins and macrophage subpopulations, compared to the conditions before irradiation and directly after irradiation with 60 Gy.