Developmental psychologists have long been concerned with the ways that early adversity influences children's long-term outcomes. In the current study, activity of the hypothalamic-pituitary-adrenal axis of medically at-risk (e.g., preterm) infants was measured as a result of maternal participation in a novel cognitively based home visitation program (versus a Healthy Start home visitation program). Maternal participation in the cognitive intervention predicted lower basal cortisol levels among infants--with reduced levels of maternal avoidance/withdrawal serving as a mediator of this relation. Lower cortisol levels in infancy, in turn, predicted higher verbal short-term memory (STM) at age 3. STM represents a cognitive ability that has importance for children's later educational outcomes. Findings provide experimental evidence concerning the pathway by which an early intervention may produce hormonal changes that can, in turn, influence children's learning outcomes.