Pseudorabies virus (PRV) was inoculated by various routes into sixteen dogs; four other dogs comprised a control group. Electrocardiograms and serum samples for lactate dehydrogenase (LDH) and creatine kinase (CPK) isoenzymes were taken twice daily. Upon death, the dogs were examined to determine the relationship of PRV to the development of heart lesions. Abnormal electrocardiograms displaying transitory and persistent arrhythmias were consistent findings, along with various myocardial lesions in these same dogs. Ganglioneuritis of the stellate ganglion was another common finding. Herpes-like intranuclear inclusion bodies were found by electron microscopy in many neurons and satellite cells of ganglia associated with the autonomic nervous system and in endothelial cells. No viral inclusions were found in myocardial cells. PRV could be isolated from oral and nasal secretions of only one dog. Significant increases in LDH-1 were noted but not with CPK-MB. It was concluded that PRV caused myocardial lesions by producing marked ganglioneuritis of stellate and cardiac ganglia and by endothelial disruption. These lesions then initiated arrhythmias resulting in sudden death.