The central nervous system regulates cardiovascular homeostasis through the actions of sympathetic nerves. Sympathetic nerve activity is elevated in cardiovascular disease including myocardial infarction (MI). Sympathetic nerve activity is the output from brain nuclei that receive inputs from a multitude of peripheral sites. How the brain nuclei are involved in facilitating the sympathoexcitation occurring after MI and its progression to heart failure is unclear. Functional studies indicate that within the paraventricular nucleus of the hypothalamus (PVN), nitric oxide (NO) is responsible for a sympathoinhibitory action on sympathetic nerves and alteration of this may be responsible for the sympathoexcitation manifest in heart failure (Li & Patel, 2003). This investigation sort to correlate PVN neurochemical change after MI to identify which neurones are involved in the sympathoexcitation. The University of Auckland Animal Ethical Committee approved all experiments. Male Wistar rats were anaesthetised with isoflurothane (4% in 2.5l/min O2). A left intercostal thoracotomy was performed to expose the heart, the pericardium was removed and the left coronary artery ligated. In the sham group the chest was opened, pericardium removed with no ligation of the coronary artery and in control no intervention was performed. Animals recovered for 3 weeks, when they were re-anesthetised (pentobarbitol 60mg/kg) and an echocardiograph performed to assess cardiac function. Following this animals were humanely killed (pentobarbital, 60mg/kg), perfused-fixed (4% paraformaldehyde) with removal of brain and spinal cord. Frozen sections (40μm) were incubated in goat anti c-Fos followed by biotinylated donkey anti goat IgG then strepavidin Alexa Fluor 594. Sections were incubated in rabbit anti nNOS then goat anti rabbit Cy2. The tissue was examined under epifluorescence. Fractional shortening, (measure of left ventricular function) for MI was less than half that of control and sham animals (MI: 19.5±0.9% SE, n=3, Sham: 48.5±5.7% SE n=5, Control: 49.3±6% SE n=4). Heart weight for MI was larger than that for control and sham (MI: 1.8±0.1g SE n=3, Sham: 1.4±0.1g SE n=5, 1.3±01g n=4). For sham and control, Fos immunoreactive (FOS-IR) neurones were localised to the parvocellular regions of the PVN. For the MI group, FOS-IR neurones were concentrated in the dorsal cap, a region involved in regulation of renal sympathetic nerve activity (Deering & Coote, 2000). Neuronal nitric oxide expression within the PVN was consistent across the groups. These preliminary findings suggest 3-weeks after MI, neurones in the dorsal cap of the PVN appear to be preferentially activated. This may represent a state where neurones in the dorsal cap drive sympathetic activity but are still under the inhibitory influence of NO.