Electrical stimulation of the hypothalamus in rats anesthetized with chloralose-urethane evoked antidromic responses in 5% of the neurons in the nucleus tractus solitarius (NTS) which responded orthodromically to vagus nerve stimulation. The NTS neurons with such a direct forebrain projection (F-NTS neurons) were distributed mostly in the lateral part of the ipsilateral commissural NTS. Latencies of the antidromic responses ranged from 20 to 75 ms, indicating that the axons of the F-NTS neurons were unmyelinated. Orthodromic responses (latencies, 20 to 80 ms) were observed in 6 of 23 F-NTS neurons, to the same stimuli that evoked the antidromic responses. Sites that elicited antidromic responses in the F-NTS neurons upon stimulation covered almost all medial hypothalamic nuclei, but 65% were localized in the preoptic-anterior hypothalamic region. All orthodromic responses to activation of vagal afferent fibers (either myelinated or unmyelinated) were polysynaptic in nature. Three F-NTS neurons were found to project to two different hypothalamic regions, by axonal branching. In addition, the firing rate of most F-NTS neurons was not appreciably affected by norepinephrine-induced blood pressure increase. It is concluded that vagal visceral input is transmitted polysynaptically to the F-NTS neurons and is then conveyed to the forebrain via the direct pathway.