Mammary epithelial cells (MEC), that produce milk, are shed into milk during the lactation process. We propose the estimation of MEC exfoliation rate into milk as an original trait to characterize the lactation persistency of dairy cows. We developed a non-invasive method to determine this rate through milk MEC purification by an immuno-magnetic method. The rate of MEC exfoliation into milk was determined in two trials where lactation persistency of Prim’Holstein cows was affected. In the first study, 14 cows were ovariectomized or sham-operated around 60 days in milk. Milk was collected at 5, 21, 37, 47 and 54 weeks of lactation to estimate MEC exfoliation rate. Milk yield decreased as lactation progressed (P<0.05) and the number of MEC daily exfoliated into milk tended to increase (P<0.10). Ovariectomy reduced by 8.1% the decline of milk yield (P<0.05) and decreased MEC loss in milk at 47 weeks (P<0.05). In the second study, 9 cows were assigned to 3 treatments during 3 5-d periods: (1) daily injections of Quinagolide (Quin), a prolactin-release inhibitor; (2) daily injections of Quin and injections of prolactin (PRL); (3) daily injections of vehicles as control. Quin decreased milk yield (P<0.05) and increased the MEC loss into milk (P<0.05). PRL injections did not restore milk yield but tended to reverse the effect of Quin by increasing milk protein content (P<0.10) and decreasing the milk MEC content (P=0.10). Our results showed that less MEC exfoliation into milk was associated with a greater lactation persistency in ovariectomized cows and that PRL could regulate MEC exfoliation. A large scale study is now necessary to determine if MEC exfoliation rate into milk is a phenotype that could characterize the ability of cows for a high lactation persistency.