The gammaherpesviruses include the human pathogens Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV, or HHV-8) (for review, see references 10 and 18). These viruses establish lifelong infection of the host and are associated with a number of malignancies. To better understand gammaherpesvirus pathogenesis, we and others have begun to utilize infection of mice with murine gammaherpesvirus 68 (␥HV68, also referred to as MHV-68) (23, 37). ␥HV68 is a member of the gamma 2 -herpesvirus subfamily based on genome sequence (7,8,13,35).The pathogenesis of ␥HV68 has been reviewed recently (21,23,26,37). Briefly, ␥HV68 infection of inbred mice results in an acute, productive infection of multiple organs and a CD4 ϩ