Two day old piglets were inoculated intravenously with 1 ml of swine vesicular disease virus UK-G 27-72 isolate. Using infectivity tests, immunofluorescent staining and gross and histopathological examination, pathogenesis of the infection was studied in tissue specimens collected daily from one through seven days postinoculation. Swine vesicular disease virus had a strong affinity for the epithelia of the tongue, snout, coronary band and lips, the myocardium and the lymphoid elements of the tonsil and the brain stem. The virus had the greatest affinity for the epithelium of the tongue. However, there was no evidence that the tongue was the initial replication site for swine vesicular disease virus. Prickle cells in the stratum spinosum appear to be the primary targets for the virus. The necrotic foci in the stratum spinosum appeared first, followed the next day by reticular degeneration and multilocular intraepidermal vesicular formation. In the digestive tract and most of the other visceral organs the short duration and sudden drop of the virus titres and the negative fluorescence and pathological findings suggest that these are not important sites for the replication of swine vesicular disease virus in this experiment. The virus was recovered from most of the central nervous tissue specimens. Although the piglets had significant central nervous system lesions, signs of impaired central nervous system function were not detected. However, subtle nervous signs could have been obscured by difficulties in locomotion resulting from severe lesions of the feet.