HL-60 cells can be induced to differentiate into macrophage-like cells by treatment with 12-O-tetra-decanoylphorbol-13-acetate (TPA). The relationship between virus replication and cell differentiation was investigated using HL-60 cells that had been induced to differentiate by TPA (dHL-60 cells) and undifferentiated cells (udHL-60 cells). On infection of these cells with cell-free varicella-zoster virus (VZV), virus antigens were detected in dHL-60 cells but not in udHL-60 cells, and the percentage of antigen-positive dHL-60 cells increased during incubation. Similar results were obtained by infectious center assay, and the percentage of antigen-positive cells correlated with the stage of cell differentiation. No significant difference was found in the binding of VZV to dHL-60 cells and udHL-60 cells. Furthermore, trypsin treatment after adsorption suggested that VZV penetrated into udHL-60 cells. These findings indicate that VZV may be able to replicate in mature monocytes but may be harbored in immature monocytes in vivo.