The purpose of this study was to describe the distribution patterns of various leukocyte subpopulations in the oral mucosa during the course of radiotherapy and to determine whether there are dose-dependent alterations, or any correlation between the clinical stages and the population density of specific leukocytes. The distribution and density of various leukocytes in oral mucosa in 13 head and neck cancer patients were immunohistochemically analysed before radiotherapy at 30 and 60 Gy and compared with the clinical degree of oral mucositis. Antibodies were used which characterized different subtypes of macrophages (27E10, 25F9, RM3/1) and recognized epitopes of granulocytes (CD15) and T cells (CD3, CD4, CD8). The study showed that whereas macrophages reactive with RM3/1 increased significantly at 30 Gy (p<0.01) and showed a further increase at 60 Gy (p<0.01), no significant alterations could be detected in the density of macrophages which stained positively for 27E10 or 25F9. Moreover, the percentage of macrophages reactive with RM3/1 showed a non-linear correlation with the clinical mucositis score (p<0.05). No significant alterations were detected in the percentage of T cells and granulocytes, compared with the values before radiotherapy. In conclusion, radiation-induced mucositis is characterized by features of an intermediate stage of an inflammatory response, suggesting active involvement of down-regulatory macrophages in its pathogenesis. Copyright © 2000 John Wiley & Sons, Ltd.