In the CNS, endomorphin 1- and endomorphin 2-immunoreactive neuronal cell bodies have been principally found both in the hypothalamus and nucleus tractus solitarii. Functionally, the hypothalamus and nucleus tractus solitarii are closely related in many aspects, especially in visceral functions. On the other hand, there are also many endomorphin-immunoreactive fibers and terminals in the two regions. In the present study, to investigate whether endomorphin 1-immunoreactive and endomorphin 2-immunoreactive neurons in the hypothalamus and nucleus tractus solitarii project reciprocally between these two regions, fluorescent retrograde labeling combined with immunofluorescence histochemical staining for endomorphin 1 and endomorphin 2 was used. After injection of Fluoro-Gold into the nucleus tractus solitarii of rats, endomorphin 1/Fluoro-Gold or endomorphin 2/Fluoro-Gold double-labeled neuronal cell bodies were predominantly observed in the arcuate nucleus of the hypothalamus, a few of which were also observed in the posterior hypothalamic area and periventricular hypothalamic nucleus. After injection of Fluoro-Gold into the medial zone of hypothalamic tuberal region and the lateral hypothalamic area, respectively, endomorphin 1/Fluoro-Gold or endomorphin 2/Fluoro-Gold double-labeled neuronal cell bodies were found chiefly in the medial, commissural, lateral and gelatinous parts of the nucleus tractus solitarii. These results provide morphological evidence that there exist reciprocal endomorphinergic connections between the hypothalamus and nucleus tractus solitarii.