Sequential effects on cellular protein expression following human immunodeficiency virus (type 1) infection of a CD4+ T-cell line in vitro were investigated. Events in the human interleukin 2-dependent helper T-cell line WE17/10 are similar in several respects to the clinical progression in acquired immunodeficiency syndrome. WE17/10 cell infection is characterized by an extended period during which viral replication occurs without accompanying cytotoxicity and with a maximum 30% decrease in surface CD4. Cellular protein expression generally remains unaffected during this first phase of infection. However, after 2-3 months, a severe defect in the expression of the T-cell receptor/CD3 complex both on the cell surface and inside the cell becomes apparent. Other cell membrane markers, such as CD2 and CD25, remain constant throughout the course of infection; after its initial decrease, CD4 remains at 70% of control values. Lack of surface expression of the TCR/CD3 complex is correlated with a specific defect in transcription of the CD3 gamma-chain gene.