Clinical studies indicate the predominance of psychosocial factors (nurturing environment) in the genesis of the Maternal Deprivation Syndrome. Consequences of disrupting mother-infant interactions range from marked suppression of certain neuroendocrine and physiological systems after short periods of maternal deprivation to retardation of growth and behavioral development after chronic periods. We have shown that maternal separation initiates a complex adaptive biobehavioral response in preweaning rat pups that includes (1) a decrease in the synthesis of ornithine decarboxylase, an obligatory enzyme for normal cell growth and development, (2) a reduction in DNA synthesis, an index of cell multiplication, (3) abnormal patterns of neuroendocrine secretion, and (4) a suppression of cell responses to growth hormone, prolactin and insulin, three major trophic hormones. This unique pattern of adaptation to maternal separation is not related to food or temperature changes but results from a lack of a specific type of tactile stimulation of the pup by the mother. Recently, we have shown that in the absence of "nurturing touch" the brain initiates the suppression of ornithine decarboxylase gene transcription by interfering with the cell's ability to transduce the activating signal induced by the growth promoting hormones. Studies indicate that central endorphinergic pathways may mediate this action. This is accomplished by the downregulation of specific Immediate Early Genes (c-myc and max) that normally promote the synthesis of this critical growth-regulatory enzyme. These studies of short-term maternal separation not only demonstrated that maternal care is a critical regulator of pup physiology and biobehavioral development but that there are marked similarities between this animal model of maternal separation and the delay in growth and development observed in children with the deprivation syndrome or in touch-deprived premature human neonates. Our identification of a specific type of nurturing touch as a neonatal growth requirement led us to test supplemental tactile stimulation in isolated very-premature human babies. The result of our intervention with massage was dramatic. Infants not only showed marked gains in weight and behavioral development, but also a significant enhancement in sympatho-adrenal maturation. We suggest that animal models of maternal deprivation can be used to understand the integrative processing of appropriate sensory input, CNS function and end-organ physiology required to maintain normal development.