The splenorenal reflex induces changes in mean arterial pressure (MAP) and renal function. We hypothesized that, in addition to the spinal pathways previously identified, these effects are also mediated through central pathways. We investigated the effect of elevated splenic venous pressure on central neural activation in intact, renal denervated, and renal+splenic denervated rats. Fos labeled neurons were quantified in the nucleus of the tractus solitarius (NTS), the paraventricular nucleus (PVN), the supraoptic nucleus (SON) and the subfornical organ (SFO) after 1hr partial splenic vein occlusion (SVO) in conscious rats bearing balloon occluders around the splenic vein, telemetric pressure transducers in the gastric vein (splenic venous pressure), and abdominal aorta catheters (MAP). SVO stimulated Fos expression in the PVN and SON, but not the NTS or SFO of intact rats. Renal denervation abolished this response in the parvocellular PVN, while renal+splenic denervation abolished activation in the magnocellular PVN and the SON. In renal-denervated animals, SVO depressed Fos expression in the NTS and increased expression in the SFO, responses which were abolished by renal+splenic denervation. In intact rats, SVO also induced a fall in right atrial pressure, an increase in renal afferent nerve activity, and an increase in MAP. We conclude that elevated splenic venous pressure does induce hypothalamic activation, and that this mediated through both splenic and renal afferent nerves. However, in the absence of renal afferent input, SVO depressed NTS activation, probably as a result of the accompanying fall in cardiac preload and reduced afferent signalling from the cardiopulmonary receptors.