The effect of local tissue temperature on bovid herpesvirus 2 lesions in bovine skin was studied. Two areas of thoracic skin were multiply inoculated with virus and maintained at different temperatures; one above and the other below the rectal temperature of the animal. An entire inoculation site was removed daily from each area and subjected to virus, viral antigen, and interferon titrations and both light and electron microscopic examinations. Lesions in cold skin appeared sooner after inoculation, were larger and deeper, contained more infectious virus, viral antigen, and interferon, and lasted longer than lesions in hot skin. Differences in viral titers greater than 10(9) 50% tissue culture infective doses per gram were measured on postinfection days 5 to 9. These studies have demonstrated for the first time that temperature effects on viral pathogenesis may operate at the local level rather than by systemic modification of immune responses. The results also suggest that despite the presence of virus in internal organs of bovid herpesvirus 2-infected cattle and the ability of bovid herpesvirus 2 to replicate to very high titers in these tissues in vitro, only the skin is cool enough to permit substantial viral replication and dermal lesions in vivo. The observed restriction of bovid herpesvirus 2 skin lesions to the udder and teats of cattle and the restriction of outbreaks of disease to months when the temperature is declining may also be reflections of this temperature sensitivity.