The neutralization of human cytomegalovirus (HCMV) after adsorption to the cell surface at 4 degrees C was studied using two neutralizing monoclonal antibodies (C-23 and C-41) recognizing glycoprotein 130/55. HCMV adsorbed to cells was neutralized by C-23 (complement-independent), but not by C-41 (complement-dependent). Furthermore, the virus remained sensitive to C-23 for 120 min after shifting up from 4 degrees C to 37 degrees C, suggesting that C-23 might block an early stage of virus penetration into cells, and also that transition from virus attachment to virus penetration might be quite slow. The cell-to-cell infection of HCMV was also blocked only by C-23, and not by C-41. On the basis of the results presented here, we suggest that C-41 blocks the attachment of virus to the cell surface whereas C-23 prevents the penetration of virus into the cell.