Mucositis is a frequent problem after irradiation of the oral mucosa. To study the early effects of irradiation on the desmosomal adhesion complex, explants of keratinized oral mucosa were exposed to a single dose of 2 Gy gamma irradiation. Biopsies were obtained from the upper dental arch of nine young healthy non-smoking women undergoing minor oral surgery. The biopsies were incubated in a Transwell culture system and, after irradiation, fixed in formalin 24 h later. Morphometric measurements of epithelial thickness revealed that it was unaffected by exposure to ionizing rays. Immunofluorescence analysis of desmosomal cadherin expression (desmoglein 1/desmoglein 3) demonstrated that the distribution of desmoglein 1 was not affected, whereas the expression of desmoglein 3 decreased in the suprabasal layers of irradiated samples. It is suggested that this has consequences for the mechanical integrity of the mucosa and promotes the development of radiation mucositis.