There is considerable physiological evidence indicating that the medial preoptic area plays an important role in neural circuits mediating ingestive, thermoregulatory, and reproductive behaviors, all of which involve foraging. The current series of anatomical and electrophysiological experiments was therefore designed to characterize a direct projection from the medial preoptic area to a region in the zona incerta just dorsal to the subthalamic nucleus, which appears to lie within the ‘subthalamic locomotor region’, and to the pedunculopontine nucleus, which lies within the ‘mesencephalic locomotor region’. First, implants of the fluorescents tracer True blue were placed in the pedunculopontine nucleus, and retrogradely labeled neurons were consistently found in dorsal regions of the medial preoptic nucleus, anteroventral preoptic nucleus, rostral tip of the medial preoptic area, lateral parts of the medial preoptic area. and median preoptic nucleus. Second, combined retrograde-immunostaining experiments indicated that a small number of galaninstained neurons in the rostral tip of the medial preoptic area project to the pedunculopontine nucleus, whereas in nearby regions some galanin- or neurotensin-stained neurons in the lateral preoptic area, and some neurotensin-stained neurons in the substriatal gray appear to project to the pedunculopontine nucleus, as do some neurotensin- or corticotropin releasing factor (CRF)-stained cells in the bed nucleus of the stria terminalis. Third, injections of the anterograde tracer Phaseolus vulgaris leukoagglutinin (PHA-L) into various parts of the medial preoptic area all labeled axons with terminal boutons in the caudal zona incerta and pedunculopontine nucleus. Fourth, single-pulse stimuli were delivered to the zona incerta and pedunculopontine nucleus and the location of antidromically activated neurons in the medial preoptic area was mapped using extracellular recordings. Somewhat less than one-third of the cells recorded from in the medial preoptic area were antidromically activated from either site and some 14% were influenced from both sites. The application of a reciprocal collision test to a small number of neurons suggested that at least some neurons in the medial preoptic area may send collaterals to both sites. And fifth, injections of procaine into the zona incerta were shown to block the antidromic activation of medial preoptic neurons by single-pulse stimulation of the pedunculopontine nucleus. Taken together, these results suggest that neurons in discrete parts of the medial preoptic area, at least a few of which may contain galanin, send fibers to the zona incerta (near the subthalamic nucleus), and that this projection then courses posteriorly to a terminal field in the pedunculopontine nucleus. The possible role of this pathway in modulating locomotor responses is discussed.