This investigation evaluated mammary cell loss and replacement during lactation and the impact of administration of bST on these processes. During lactation, a gradual decrease in number of mammary epithelial cells within the mammary glands occurs and largely accounts for the decline in milk production with advancing lactation. This decrease is not appreciably impacted by the loss of viable epithelial cells in milk. Rather, the net decline in cell number (approximately 50% during the entire lactation) results from continual death by apoptosis. Accompanying the decline in mammary cell number by apoptosis is a degree of cell renewal. Approximately 0.3% of mammary cells in lactating, nonpregnant cows were labeled by a 24-h in vivo treatment with the thymidine analog, bromodeoxyuridine. During the entire lactation, the number of new cells amounts to approximately 50% of the number of cells initially present. By the end of lactation, most cells present in the mammary gland were formed after calving. Increasing cell replacement or decreasing apoptosis during lactation may provide a means to increase persistency of lactation. Indeed, administration of bST to Holstein cows during midlactation increased the proportion of mammary epithelial cells expressing the nuclear proliferation antigen, Ki-67, from 0.5 to 1.6%. Bovine somatotropin appears to increase the rate of cell renewal in the lactating mammary gland. Knowledge of molecular regulation of apoptosis and cell proliferation should provide a means to modulate cell turnover in the mammary gland. A change in the ratio of epithelial proliferation to cell death during lactation will affect the persistency of lactation.