ObjectiveTo describe how an animal model system can be used to explore basic questions about the nature of loss and the effects of early loss on later vulnerability to disease.MethodThe physiological and behavioral responses of infant rats to separation from their mothers are first described and then analyzed experimentally into component mechanisms.ResultsThese studies have revealed an extensive layer of processes underlying the psychological constructs generally used to understand the response to loss. Hidden within the observable interactions of parent and offspring, we found a number of discrete sensorimotor, thermal, and nutrient-based events that have unexpected long-term regulatory effects on specific components of infant physiology and behavior. Release from all of these inhibitory and excitatory regulators together during maternal separation constitutes a novel mechanism by which the experience of loss can be translated into a complex patterned response. Evidence for early regulatory processes has also been found in monkey and human mother-infant interactions. Here they may well constitute the building blocks from which attachment and object representations develop. We and others have found long-term effects of loss, and of selective replacement of regulators, on behavioral development and on later vulnerability to disease.ConclusionsThe results give us a new understanding of early attachment as a developmental force and of human grief as a risk to health.