The pathogenesis of endometriosis, a disease widely believed to arise from an aberrant growth of endometrial tissue outside the uterus, is still unclear. We have previously observed that cytokine-stimulated endometrial cells of women with endometriosis secrete in vitro increased amounts of monocyte chemotactic protein-1 (MCP-1). This factor may be important in the recruitment and activation of peritoneal macrophages observed in endometriosis patients. The present study reports that, in the presence of the disease, such an up-regulation of MCP-1 expression arises in vivo and can be encountered in situ in the intrauterine endometrium. In women with endometriosis, MCP-1 expression was elevated in endometrial glands, both at the level of the protein (immunohistochemistry) and the mRNA (in situ hybridization). This was observed throughout the menstrual cycle and varied according to the stage of the disease. These findings strongly argue in favor of the presence of pathophysiological changes in the eutopic endometrium of patients with endometriosis and make plausible MCP-1 as a key effector cell mediator involved in the pathogenesis of the disease.