The growth of herpes simplex virus (HSV) type 1 in human lymphoid cell lines, arrested at various stages of differentiation, was studied. The synthesis of viral DNA and antigens and the production of infectious virus were followed in null, B and T leukemia-lymphoma cell lines. It was found that while "nondifferentiated" null cells and cells differentiating along the B pathway, even at very early stages of differentiation, supported HSV growth, cell lines of T origin at all stages of differentiation were generally nonpermissive. The failure of T cells to support the growth of HSV did not result from inefficient adsorption to the host cells. However, viral DNA synthesis was not detected, and a significant reduction in the ability of synthesize HSV antigens was observed. It is suggested that the block in the growth cycle of the virus occurs at a stage after adsorption of the virion to the cells, but prior to synthesis of its DNA and proteins.