The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein is synthesized as a precursor glycoprotein, gp160, and is then processed into gp120 and gp41. In the present study, CD4+ cell clones expressing either gp160 or gp120 of HIV-1 under the transcriptional control of an inducible promoter were made in order to examine the effect of these env products on the downregulation of surface CD4 and cell injury. A complete disappearance of surface CD4 preceding single-cell death occurred in the cell clones expressing gp160, in which a complex between CD4 and gp160 was formed and then accumulated intracellularly. In contrast to this, the cell clones expressing gp120 neither exhibited any such depletion of surface CD4 nor showed any apparent cytopathic effect. Therefore, it is thought that gp160 but not gp120 plays a crucial role in both the downregulation of surface CD4 and the resultant cell death in the cells infected with HIV-1.