Milk yield is partly influenced by the number of mammary epithelial cells (MEC) in the mammary gland. It is well known that MEC number varies due to cell proliferation and apoptosis. The exfoliation of MEC from the mammary epithelium into milk is another process which might influence MEC number in the mammary tissue. Yet, little is known about the control of MEC exfoliation process. The rate of MEC exfoliation can be assessed by measuring the milk MEC content through flow cytometry analysis or through an immuno-magnetic method for MEC purification. Various experimental models were used to affect milk yield and study the rate of MEC exfoliation. Reducing milking frequency from twice to once daily increased MEC loss per day in goat but not in cow milk. An increased daily rate of MEC exfoliation was also observed during short days as compared with long days or in response to an endotoxin-induced mastitis in cows. Other animal models were designed to investigate the endocrine control of the exfoliation process and its link with milk production. Suppression of ovarian steroids by ovariectomy resulted in a greater persistency of lactation and a decrease in MEC exfoliation. Administering prolactin inhibitors enhanced MEC loss while exogenous prolactin tended to prevent this negative effect of prolactin inhibitors. These findings suggest that prolactin could regulate MEC exfoliation. In most of these studies, variations of MEC exfoliation were associated with variations in milk yield and changes in mammary epithelium integrity. Exfoliation of MEC could be a process that regulates MEC number in the mammary tissue, and thereby could influence milk yield and lactation persistency.