The effect of peripheral blood mononuclear cells (PBMC) on expression of varicella-zoster virus (VZV) glycoproteins (Gps) was analyzed by flow cytometry. PBMC from VZV seropositive and seronegative donors and supernatant of PBMC co-cultured with VZV-infected human embryonic fibroblasts reduced VZV Gp expression. Neutralization of supernatant fluid with mixture of anti-interferons (IFN)-alpha, -beta, -gamma, and tumor necrosis factor (TNF)-alpha partially reduced inhibitory activity of supernatant on VZV Gp expression. Deletion of natural killer (NK) cells and adherent cells from PBMC reduced inhibitory activity of PBMC on VZV Gp expression. These results suggest that IFN-alpha, -beta, -gamma, TNF-alpha and other soluble factors released from NK cells and monocytes by co-cultivation with VZV-infected fibroblasts inhibit VZV Gp expression.