Based on our findings that HIV-1 gp41 independently of CD4 can bind to the human helper T lymphoid cell line H9, B cell line Raji and monocyte cell line U937, we characterized putative binding of HIV-1 gp41 to human peripheral blood lymphocytes (PBLs) and monocytes. Using flow cytometry (FACS), we demonstrated that the recombinant soluble HIV-1 gp41 (sgp41; Env amino acid 539-684) can bind to the normal human peripheral blood mononuclear cells (PBMCs), preferentially to B lymphocytes and monocytes independently of gp120-binding sites on CD4 molecules. This binding is dose-dependent. The HIV-1 sgp41 binds to blood B lymphocytes and monocytes more strongly than to T lymphocytes. By two-color flow cytometric analysis, we identified that sgp41 can bind 10 % of CD4+ T lymphocytes, 11.9 % of CD8+ T lymphocytes, 47 % of CD19+ B lymphocytes and 44.2 % of CD14+ monocytes.