A defect in the cytolytic activity against autologous endometrial cells refluxed in the peritoneal cavity has been hypothesized as being involved in the etiology of endometriosis, although its causes have not been definitively identified. Cell adhesion molecules are necessary not only for cell-to-cell contact but also for the binding of immune effectors to their targets. In this study, the expression of CD54, CD58 and CD106, three adhesion molecules with a crucial role in cytotoxic mechanisms, was quantitatively studied on fresh endometrial cells by immunofluorescence and flow cytometry. Samples were collected from endometriosis patients (n=10) and controls (n=12), either during the follicular or luteal phase of the cycle. While no significant differences were observed for CD58 and CD106, a significantly reduced expression of CD54 in the secretory endometrial cells of women with endometriosis was observed (-75% with respect to apparently healthy controls). These findings could account for an apparently cyclic defect in the expression of CD54 that could result in poor binding of immune effectors to secretory endometrial cells in vivo. The defective recognition and removal of refluxed endometrial cells could, at least in part, be involved in the pathogenesis of endometriosis.