The present study describes the anatomical organization of projections from functionally defined cell groups of the lateral hypothalamic area. Cardiovascular pressor and depressor sites were identified following microinjection (5-50 nl) of 0.01-1.0 M L-glutamate or D,L-homocysteate into the anesthetized rat. Subsequent injections of Phaseolus vulgaris-leucoagglutinin (PHA-L) or wheat germ agglutinin-horseradish peroxidase (WGA-HRP) were made into pressor or depressor sites and their connections with the brainstem and spinal cord were traced. Decreases in blood pressure (10-45 mmHg) and heart rate (20-70 bpm) were elicited from tuberal (LHAt) and posterior (LHAp) regions of the lateral hypothalamic area (LHA). Depressor neurons in the LHAt have descending projections to the central gray, dorsal and median raphe nuclei, pedunculopontine tegmental nucleus, pontine reticular formation, medial and lateral parabrachial nuclei, laterodorsal tegmental region, and medullary reticular formation including the region of the lateral tegmental field, nucleus ambigous, and rostrocaudal ventral lateral medulla. In contrast, descending projections from depressor neurons in the LHAp have dense terminal fields in the rostral, middle, and commissural portions of the nucleus of the solitary tract and the lateral tegmental field as well as the ventrolateral central gray, pedunculopontine tegmental nucleus, and medial and lateral parabrachial nuclei. Both the LHAt and LHAp have light projections to the intermediate region of the cervical and thoracic spinal cord. Increases in blood pressure (10-40 mmHg) and heart rate (20-70 bpm) were elicited almost exclusively from neurons located medial to the LHAt and LHAp in a region surrounding the fornix, termed the perifornical area (PFA). Pressor cells in the PFA have descending projections to the central gray, dorsal and median raphe nuclei, laterodorsal tegmental nucleus, and Barrington's nucleus as well as a light projection to the commissural portion of the nucleus of the solitary tract and the intermediate region of the cervical and thoracic spinal cord. The retrograde labeling observed in the WGA-HRP studies indicates that cells in most terminal fields have reciprocal projections to the pressor and depressor regions of the LHA. The results demonstrate that groups of neurons in the lateral hypothalamus with specific cardiovascular function have differential projections to the brain stem.