AbstractSince viral infection is in most cases contrary to the survival of the host cell, it is reasonable to assume that cells possess innate viral replication inhibitory mechanisms. Even between strains of permissive cells, degrees of permissiveness are observed. Restriction to human cytomegalovirus (CMV) replication in vitro is well known, especially in epithelioid cells or cells derived from certain organs. We have studied restriction in a fibroblastic strain of human embryonic kidney cells. By treatment of cell cultures with maximum physiologic concentration of the hormone cortisol (25 μg%) both pre and post virus inoculation, susceptibility to laboratory strain Ad169 CMV and low‐passaged clinical isolate JSS CMV was enhanced by factors of 6.4 ± 0.7 and 11.1 ± 0.4, respectively; effectively converting these cells to a totally permissive state. A linear dose response, which peaks at 25 μg% and declines thereafter up to 300 μg%, is evident for both virus strains in this enhancement system. Breakdown of restriction increases in linear fashion with increasing time of cortisol pretreatment of cells. The characterization of cortisol effects converting restrictive human fetal cells in vitro to the permissive state further indicates that human hormones may play a significant role in CMV susceptibility i