In human immunodeficiency virus type 1 (HIV-1)-infected adults, the proportion of gp120-free CD4 molecules on the surface of T lymphocytes was measured by double-epitope EIA and expressed as a CD epitope concentration ratio. In 51% of these patients (n=81), CD4 T cells showed a significant decrease (up to 100%) in the accessibility of the CD4 epitope in the D1 domain remained accessible. Of interest, a significant increase in the CD4 gp120 binding site concentration, without a change in T cell counts, was observed within 10 days after initiation of zidovudine treatment. Furthermore, CD4 masking by gp120 was associated with a poor clinical patient status. The assessment of the CD4 epitope concentration ratio is proposed as a surrogate marker of disease progression in HIV-1-infected patients.