The UL18 open reading frame of human cytomegalovirus (HCMV) (which encodes a product homologous to major histocompatibility complex class I heavy chains) has been disrupted by insertion of the beta-galactosidase gene under control of the major HCMV early promoter. The recombinant virus delta UL18 showed no phenotypic differences from wild-type HCMV in terms of single-step growth curves or particle/infectivity ratios, indicating that the UL18 gene product is dispensable for the growth of HCMV in human fibroblasts in vitro. The synthesis of the mature cellular class I heterodimer is shut down in cells infected at a high multiplicity with wild-type HCMV, and a similar effect was seen in delta UL18-infected fibroblasts, suggesting that although the UL18 gene product can associate with beta 2 microglobulin, it is not directly involved in the disruption of class I assembly.