Dysfunction of parasympathetic command neurons may be a cause of cardiac autonomic imbalance, which has been implicated as a pathogenic mechanism of lethal arrhythmias. The locations in the brain of these command neurons are not known. The aim of this investigation is to identify selectively the parasympathetic command neurons in the forebrain. Male Wistar rats were inoculated in the left ventricular myocardium with 2 ml of a 3 x 10(6) plaque-forming units/ml of a pseudorabies virus (PRV)-Bartha solution. Eighteen hours after the infection, the spinal cord was transected at T1. Six of fourteen rats showed PRV-immunoreactive cells in the forebrain after 6 postoperative survival days. Bilaterally, the infections were located in the prelimbic, anterior cingulate, frontal, and insular cortexes, various hypothalamic and midbrain nuclei, the nucleus of the solitary tract, the dorsal motor vagus, and periambiguus nuclei. Control animals receiving intravenous PRV-Bartha injections were not infected. Using transneuronal retrograde viral labeling and spinal cord transection, we were able to localize the forebrain parasympathetic command neurons that maintain cardiac autonomic balance. The virus-infected cells were localized in regions that previously showed susceptibility for immune activation-mediated selective cerebral endothelial leakage. We hypothesize that such selective endothelial leakage could induce autonomic imbalance after myocardial infarction.