Homeostasis during lactation is a special case in which the unit of homeostatic regulation is not a single organism, but rather a dyad comprising the mother and her offspring (the mother–infant dyad). This dyadic arrangement is not trivial. The familiar laboratory mouse model system includes a mother and litter of infants whose mass can easily exceed the mass of the mother. Some physiological variables, such as body temperature, can remain under conventional homeostatic control within the individual. But other variables such as milk secretion, appetite, and calcium metabolism must come under control of the mother–infant dyad. Prolactin is the primary systemic component of mammary homeostasis. Suckling inhibits dopamine, which induces reflex prolactin secretion in response to nursing. Other factors, such as oxytocin and endorphins increase prolactin output, which sustains enhanced prolactin throughout lactation. In addition to the systemic homeostasis, local homeostatic mechanisms control mammary gland functions. The sophistication of intramammary homeostatic mechanisms is perhaps best illustrated in kangaroos in which individual mammary glands produce different volumes and compositions of milk because they are being nursed by offspring of different ages. The millions of alveolar sacs that comprise the mammary glands are capable of independently regulating their milk outputs in response to local conditions. Most obviously, each alveolus must regulate its secretory output in response to the degree of filling. Serotonin was discovered as a primary regulator of mammary homeostasis. Serotonin synthesis is in the mammary epithelium is elevated during lactation, and increases during milk stasis. Two important functions have been attributed to the intramammary serotonin system. First, when alveolar spaces are filled with milk serotonin inhibits milk secretion and causes tight junction opening. Ultimately, this feedback system induces early phases of involution. Second, serotonin induces secretion of parathyroid hormone-related peptide (PTHrP), which is the primary regulator of calcium homeostasis for the mother–infant dyad. These 2 intramammary homeostatic responses are mediated by different receptors. Feedback inhibition of milk secretion is mediated by 5-HTR7, which is autoinhibited and requires sustained occupation to become activated. PTHrP secretion is mediated by 5-HTR2B receptors, which are activated at tonic levels of serotonin.