The SF strain of human herpesvirus 6 (HHV-6SF) isolated from the saliva of a human immunodeficiency virus (HIV)-infected individual was shown to inhibit HIV type 1 (HIV-1) replication in both peripheral blood mononuclear cells and purified CD4+ lymphocytes. This suppression of HIV-1 replication led to decreased cytopathic effects of HIV-1 and prolonged survival of CD4+ cells in culture. Even low levels of HHV-6 added to peripheral blood mononuclear cells showed an inhibitory effect on HIV-1 replication. These results differ from those previously reported showing enhanced HIV-1 production following infection with another strain of HHV-6.