Nine human monoclonal antibodies (MAbs) with neutralization activity against cytomegalovirus (CMV) were obtained by screening human MAbs using a CMV glycoprotein complex of 130 and 55 kDa (gp130/55). The gp130/55 antigen was purified by immunoaffinity chromatography and the purified antigen used to detect anti-gp130/55 MAbs in an enzyme-linked immunosorbent assay. Relatively few of the human anti-CMV MAbs were directed against gp130/55 but all showed high neutralization activities to a variety of clinical isolates with titers (ED50 values) ranging from 0.15 to 7.9 micrograms/ml. Six of the nine anti-gp130/55 MAbs required complement for virus neutralization. Such human MAbs may prove to be useful for passive immunotherapy against CMV infection.