Two human cytomegalovirus (HCMV) virion structural proteins and their associated reading frames have been identified with two human-derived monoclonal antibodies (HMAbs), X2-16 and X-16. HMAb X2-16 identified recombinant protein expressing molecular clones that mapped to the open reading frame (ORF) of the UL48 gene of HCMV, between amino acids 584 and 646 (nucleotides 65,084 and 65,272, Chee et al., 1990, "Current Topics in Microbiology and Immunology," Vol. 154, pp. 125-169). The UL48 gene product has an apparent molecular weight of 216 kDa. HMAb X-16 identified clones derived from the UL56 ORF between amino acids 380 and 425 (nucleotides 84,733 and 84,870). On immunoblots, HMAb X-16 detected two HCMV proteins of 96 and 60 kDa. Both UL48 and UL56 are highly conserved among the human herpesviruses and their products have been predicted to have essential functions for virus production and maturation. These results confirm that UL48 and UL56 are functional genes encoding essential viral proteins which also generate an immune response in the immunocompetent host.