The response in firing rate of single neurons in the cat hypothalamus to stretch of the right atrium vena caval junction. Stretch was produced by intermittant inflation of a small rubber balloon implanted between the pericardium and the wall of the right atrium. Carotid arteries were occluded bilaterally and single neurons were recorded with stereotaxically implanted microelectrodes during 10 cycles of balloon inflation. A localized area (approximately a 1.0 mmcube) was found in the posterior hypothalamus where 24 of 36 units responded to atrial stretch (13 inhibited, 6 excited, 5 off responses). Four units were tested with carotids both occluded and unoccluded. All 4 responded when the carotids were occluded, but 3 no longer responded and 1 had a markedly reduced response when the carotids were unoccluded. Stimulation of this region elicited no significant responses with currents of 40 and 75 μA for 20 sec, but currents of 200 and 400 μA for 20 sec led to significant (p<0.05) decreases in the ACTH level (radioimmunoassay) 1.5 min following the stimulus Following 200 μA stimulations ACTH returned to control levels within 15 min. In contrast, 400 μA stimulations led to sustained or further decreases in ACTH at 15-20 min (P< 0.01). The results suggest that this area may be important in the neural processing of information on blood volume, and may constitute an inhibitory pathway mediating the response of ACTH to changes in blood volume.