Recent studies have demonstrated that the metabolic hormones insulin and leptin can modulate behavioral performance in reward-related paradigms. However, specific anatomical substrate(s) within the CNS for these effects remain to be identified. We hypothesize that midbrain dopamine neurons, which have been implicated to be critical in the mediation of motivational and reward aspects of stimuli, contribute to these behavioral effects of insulin and leptin. As one approach to evaluate this hypothesis, we used double-labeling fluorescence immunohistochemistry to determine whether the midbrain dopamine neurons express insulin receptors or leptin receptors. Extensive co-expression of tyrosine hydroxylase (a marker for dopamine neurons) with both the insulin receptor and the leptin receptor was observed in the ventral tegmentum and substantia nigra. These findings suggest that midbrain dopamine neurons are direct targets of insulin and leptin, and that they participate in mediating the effects of these hormones on reward-seeking behavior.