Considerable evidence supports a role for matrix metalloproteinases (MMP) in menstruation, but their focal pattern of expression within perimenstrual and menstrual endometrium suggests local rather than hormonal regulation. Menstruation shares a number of features with inflammatory responses, with leukocyte infiltration, proliferation and activation, occurring in the endometrium prior to menstruation. We propose that the leukocytes release MMP at this time and also that interactions between leukocytes and the stromal and epithelial cells of the endometrium induce and activate MMP. Co-culture studies using mast cells or neutrophils with endometrial stromal cells support this hypothesis. How leukocytes enter the endometrium is not understood but a role for chemokines has been proposed. The expression patterns of eotaxin and its receptor CCR3 in endometrium support a role in chemoattraction of eosinophils but expression of monocyte chemotactic proteins 1 and 2 does not correlate with macrophage numbers. Nothing is known of how the leukocytes become activated. Nevertheless, the overall result is a tissue in which an inflammatory-type reaction occurs with release of a myriad of potent regulators. These induce production and activation of MMP and alter the ratio between these and their tissue inhibitors, resulting in tissue breakdown.