Electron microscopic examination of the normal oral mucosa of patients with recurrent aphthous ulceration or Behçet's syndrome revealed that the degenerate dark prickle cells are apoptotic cells. Such dark prickle cells showed characteristic findings of apoptosis, such as the shrinkage of nucleus and cytoplasm and the formation of contraction vacuoles. The number of intraepithelial mononuclear cells phagocytosing apoptotic cellular debris increased remarkably at the preulcerative stage of the aphthous lesions. The apoptotic debris also attracted neutrophilic leukocytes in the prickle cell layer at the preulcerative stage but not in the normal oral epithelium. It is speculated that the onset of aphthous ulceration is closely related to phagocytosis of these apoptotic cells by intraepithelial mononuclear cells.