The complex biology of human cytomegalovirus (HCMV) necessarily begins with an initial interaction between the envelope of the infectious virion and the host cell. Understanding the initial events of infection will require a further analysis of the glycoprotein components of the virion envelope as well as their expression in the membranes of the infected cell. This experimental goal has been hindered by the large genome of HCMV, which may encode over 65 unique glycoproteins. Protein homologs of only 4 herpes simplex virus (HSV) glycoproteins, gB, gH, gL and gM, have been identified, and potential functions have been postulated based on studies of specific glycoprotein null mutants of HSV and other herpesviruses. Additional glycoproteins have been analyzed but to date their function in the replicative cycle of this virus is unknown. Several of the envelope glycoproteins elicit strong host immune responses, including the production of virus-neutralizing antibodies. This response is felt to be a key component of host immunity and represents a goal of vaccine development. Finally, recent findings have also provided evidence that HCMV glycoproteins may contribute to evasion of host cellular immune responses by limiting viral antigen presentation. © 1996 S. Karger AG, Basel.