Since the advent of pandemic of the human immunodeficiency virus infection, the possible pathogens responsible for acute meningoencephalitis have broadened. Human immunodeficiency virus itself can cause acute meningoencephalitis, and the immunocompromise associated with human immunodeficiency virus infection predisposes the infected patients to acute meningoencephalitis caused by a variety of other infectious or non-infectious etiologies. Here reported are 2 cases of acute meningoencephalitis with history of blood transfusion and travel to southeast Asia; both are positive for screening tests of human immunodeficiency virus infection. One of the pathogen causing central nervous system infection, Mycobacterium tuberculosis, was identified by polymerase chain reaction; the other left undiagnosed. It is known that patients of human immunodeficiency virus infection or acquired immunodeficiency syndrome can present with acute central nervous system infection. The need for routine screening of human immunodeficiency virus antibody is currently under debate; nevertheless, the possibility of human immunodeficiency virus infection has to be kept in mind in patients with acute meningoencephalitis.