Prolonged maternal separation inhibits endogenous heat production in infant mammals exposed to cold. This inhibition of thermogenesis occurs many hours before energy stores have been fully depleted. The need to protect energy resources during separation-induced starvation may be signaled by declining levels of leptin, a hormone that acts as a "fat signal" and a regulator of energy utilization; in fact, starvation reduces leptin levels in adult mice and infant rats. It is not known, however, whether leptin has a functional role during starvation in infants. Such a role may be found in the regulation of nonshivering thermogenesis by brown adipose tissue (BAT), a specialized organ that provides heat to infant mammals, including humans, during cold exposure. Heat produced by BAT allows the cold-exposed infant to prevent the detrimental effects of hypothermia on physiology and behavior and, ultimately, growth. Here we show that leptin disinhibits BAT thermogenesis during cold exposure in infant rats after 18 h of maternal separation. This finding demonstrates that leptin is more than simply an adipostat for the regulation of body weight; specifically, leptin modulates thermogenesis and energy utilization in the early postnatal period.