Lactation depends on regular suckling or milkingof the mammary gland. Without this stimulus, milksecretion stops and mammary involution is induced.Involution caused by abrupt cessation of milk removal is characterized by de-differentiation andapoptosis of mammary epithelial cells, the extent andtime course of the latter varying between species.Apoptosis is inhibited and milk secretion is restored by re-suckling, if milk stasis is of shortduration. Mammary involution and apoptosis also occurduring weaning, even in concurrently-pregnant animalswhen the interval between lactations is restricted, suggesting that tissue remodeling is essentialfor subsequent lactation. Declining milk production inruminants after peak lactation is also associated with,and probably results from, net cell loss by apoptosis. Involution and apoptosis arecontrolled by changes in systemic galactopoietic hormonelevels, and by intra-mammary mechanisms responsive tomilk removal. Milk stasis precipitated by litter removal or cessation of milking may involveintra-mammary control related to physical distension ofthe epithelium. Local control of apoptosis in rodentsduring weaning, and after peak lactation in dairyanimals, may be due to the actions of milk-bornesurvival factors or their inhibitors, and can bemanipulated by frequency of milk removal.