Cytochrome oxidase histochemistry was used to evaluate neuronal changes in oxidative metabolism in response to rewarding brain stimulation of the medial forebrain bundle. Rats with single lateral hypothalamic electrodes self-stimulated daily for ten days for trains of either 0.1 or 2.0 ms pulses that corresponded to about 75% of maximum responding. Quantitative comparison of stimulated-to-unstimulated sides revealed differences in relative optical density in few structures, notably in the lateral septal nucleus and the nucleus accumbens, when the brief pulse duration was used. In contrast, the longer pulse duration gave rise to metabolic increases in several dopaminergic projections, including the frontal cortex, olfactory tubercle, and lateral habenula, and also enhanced activity in the lateral septal nucleus. These data suggest that mesocorticolimbic structures may be implicated in medial forebrain bundle self-stimulation.