Lactation depends on regular suckling or milking of the mammary gland. Without this stimulus, milk secretion stops and mammary involution is induced. Involution caused by abrupt cessation of milk removal is characterized by de-differentiation and apoptosis of mammary epithelial cells, the extent and time course of the latter varying between species. Apoptosis is inhibited and milk secretion is restored by re-suckling, if milk stasis is of short duration. Mammary involution and apoptosis also occur during weaning, even in concurrently-pregnant animals when the interval between lactations is restricted, suggesting that tissue remodeling is essential for subsequent lactation. Declining milk production in ruminants after peak lactation is also associated with, and probably results from, net cell loss by apoptosis. Involution and apoptosis are controlled by changes in systemic galactopoietic hormone levels, and by intra-mammary mechanisms responsive to milk removal. Milk stasis precipitated by litter removal or cessation of milking may involve intra-mammary control related to physical distension of the epithelium. Local control of apoptosis in rodents during weaning, and after peak lactation in dairy animals, may be due to the actions of milk-borne survival factors or their inhibitors, and can be manipulated by frequency of milk removal.