The role of the parasympathetic innervation of the left ventricle remains controversial, although there is evidence that vagus nerve stimulation decreases left ventricular contractility in vivo in the human and pig heart (1). The aim of this study was to identify the anatomical location of vagal preganglionic neurones that control ventricular contractility using an anaesthetised rat model. Male Sprague-Dawley rats (350-400g, n=6) were anaesthetised with pentobarbitone sodium (induction 60 mg/kg i.p.; maintenance 15-20 mg/kg/hr i.v.) and artificially ventilated. The left femoral artery and both femoral veins were cannulated for the measurement of arterial pressure and infusion of fluids and drugs. The right carotid artery was cannulated for left ventricular pressure recording using a Millar pressure probe. Lead II ECG was also monitored. The animal was placed in a stereotaxic frame and the dorsal surface of the brainstem was exposed. To activate vagal preganglionic neurones, an excitatory neurotransmitter glutamate (10mM, 40 nl, pH 7.4) was microinjected into three discrete locations (separated by 0.5 mm) along the rostro-caudal extent of the left and right dorsal motor nuclei of the vagus nerve (DVMN). Responses were measured in a second group (n=3) with transoesophageal atrial pacing (TAP) to abolish chronotropic changes. A third group (n=2) underwent a spinal transection at C1 to remove sympathetic influences followed by gelofusine and vasopressin infusion to maintain mean arterial blood pressure at ~100mmHg. Values are means ± S.E.M., compared by two tailed paired student’s t-test. Glutamate microinjections into the most caudal part of the left DVMN caused a significant (p<0.01) decrease in dP/dtmax (-1635 ± 301 mmHg/s), dP/dtmin (1527 ± 322 mmHg/s), mean arterial blood pressure (-27±6 mmHg) and heart rate (-15 ± 4 bpm). Glutamate had no effect on cardiovascular variables after microinjections into the rostral part of the left DVMN or after delivery into the right DVMN. With TAP, Glutamate microinjections into the most caudal part of the left DVMN caused a significant (p<0.05) decrease in dP/dtmax (-1790 ± 279 mmHg/s), dP/dtmin (1270 ± 94 mmHg/s), mean arterial blood pressure (-12±2 mmHg) and end systolic pressure (-16±2 mmHg). Responses elicited following activation of the left caudal DVMN were present after C1 transection, although they were significantly reduced by ~50%. Thus, parasympathetic control of ventricular contractility is provided by a group of vagal preganglionic neurones located in the caudal part of the left DVMN. The role of ventral groups of the brainstem vagal preganglionics (in the nucleus ambiguus) has yet to be determined.