Recently, data demonstrating that CD4 is an essential component of the receptor for human herpesvirus 7 (HHV-7) as well as for human immunodeficiency virus have been accumulating. Since gangliosides and phorbol esters are known to induce selective down-modulation of cell surface CD4 expression, it might be expected that treatment with these agents would interfere with HHV-7 infection of CD4+ T cells. The present study, undertaken to verify this possibility, demonstrated that addition of monosialoganglioside-GM1 or 12-O-tetradecanoylphorbol 13-acetate effectively induced disappearance of CD4 from the cell surface and also reduced HHV-7 infectivity, as judged by the CPE on virus-infected cells and studies of indirect immunofluorescence, TCID50 and semi-quantitative PCR of the HHV-7 genome. Taken together with previous studies, the present data strongly suggest that the CD4 molecule is a critical component of the receptor for HHV-7.