A 30-year-old bisexual male prisoner with a historyy of intravenous drug abuse manifested encephalitis. Adenovirus type 2 was isolated from brain tissue obtained by a biopsy and there was a concurrent fourfold rise in the antibody titer. In addition, an initial negative result from a slide test for infectious mononucleosis heterophil antibodies (Monospot) test converted to positive and there was an increase in the IgG antibodyy titer to Epstein-Barr virus (EBV) viral capsid antigen. Although he was anergic to skin test antigens, T-cell subsets and lymphocyte transformation study results were normal. This case demonstrated a rare adenovirus encephalitis with a simultaneous EBV infection in a patient at risk for acquired immunodeficiency syndrome, who had minimal evidence of T-cell deficiency.