The mononuclear cells in the endometrial stoma change in reactivity for lysosomal hydrolases during the menstrual cycle. Lymphoid follicles may occur in the stroma in any phase of the cycle and have been found in gestational endometrium. However, these cells have no significant lysosomal activity. Alterations in the endometrium are reflected in modified patterns of activity. Endometritis, association with an intrauterine contraceptive device, pregnancy, and adenocarcinoma result in increased numbers and staining intensity of mononuclear cells. In contrast, no consistent changes were apparent in foci of glandular hyperplasia, and decreased staining was seen in atrophic areas of endometrium. These data suggest that interstitial mononuclear cells are a sensitive monitor of morphologic changes in the endometrium.