Intercellular adhesion molecule (ICAM)-1-mediated cell-cell adhesion is essential for various immunological functions, including natural killer (NK) cell-mediated cytotoxicity against endometrium. The present study was designed to establish whether shedding of ICAM-1 from cultured endometrial stromal cells occurred and to characterize its potential functional significance in endometrial physiology and pathology. The shed sICAM-1 molecule was detected and quantified in supernatants from endometrial stromal cultures and in peritoneal fluid by a specific enzyme-linked immunosorbent assay. The results of this study indicate that cultured endometrial stromal cells constitutively shed ICAM-1 from their surface. This ability is regulated during the menstrual cycle, as it appears to be higher in the proliferative than in the secretory phase of the cycle (16.93 +/- 2.2 and 7.7 +/- 1.76 ng/ml respectively). In order to evaluate whether the release of sICAM-1 could interfere with cell-mediated lysis of endometrium we compared the determinations of sICAM-1 in endometrial supernatants with the ability of such supernatants to suppress NK cell-mediated cytotoxicity toward endometrial targets. A significant correlation (r = 0.6, P < 0.05) was found between the sICAM-1 concentration in endometrial supernatants and the percentage of inhibition of NK cell-mediated lysis exerted by the same supernatant samples. Finally, endometrial stromal shedding of sICAM-1 appears to be related to endometriosis since endometrial stromal cultures obtained from patients with advanced stages of the disease released significantly higher amounts of the soluble protein compared to the control group (P < 0.05). sICAM-1 is a soluble molecule which can interfere with immunological functions, and its shedding may be one of the mechanisms by which refluxed endometrial cells escape immunosurveillance.