To clarify some of the actions of Neurotropin (NSP), intra- and extracellular measurements were made of 140 paraventricular (PVN) and 48 ventromedial nucleus (VMH) neurons in rat hypothalamic tissue slices in vitro while perfusing NSP, an extract from the inflamed skin of rabbits inoculated with vaccinia virus, through the recording chamber. NSP mostly decreased activity in PVN neurons (inhibition, 46; excitation, 27; excitation-inhibition, 5; no response, 62), and mostly increased it in VMH neurons (excitation, 12; inhibition, 3; no response, 33). Inhibition of PVN neurons by NSP was due to hyperpolarization with no change in membrane conductance. Since ouabain antagonized the NSP-induced inhibition of PVN neurons, the effect was probably due to activation of the sodium pump. Activity of some NSP-responsive PVN neurons was increased by increase of extracellular osmolarity, and activity of some NSP-responsive VMH neurons was increased by glucose application. The results suggest central modulation of autonomic or neuroendocrinological function by distinct NSP influence on PVN and VMH neural activity.