Malignant catarrhal fever (MCF) is a severe, systemic, lymphoproliferative disease affecting domestic ruminants, caused by a group of MCF viruses in the genus Macavirus. Infection of cattle and bison with ovine herpesvirus 2 (OvHV2) is economically significant in North America. Sheep are the reservoir host of the virus, and only rarely manifest disease. Cattle and bison, however, frequently have lymphoproliferation, mucosal ulceration, and systemic vasculitis. OvHV2-induced MCF in cattle and bison is often fatal, with clinical recovery reported only rarely. Chronic cases are uncommon, but vascular changes of variable severity and ocular lesions have been described. Here we present a case of chronic MCF in a cow with proliferative arteriopathy, systemic vasculitis, and OvHV2-associated hypophysitis. We demonstrated OvHV2 nucleic acid in affected tissues with in situ hybridization.