Monoclonal antibodies (MAbs) specific for two surface glycoproteins of respiratory syncytial virus (RSV) were found to enhance RSV infection in two macrophagelike cell lines (P388D1 and THP-1). MAbs to an irrelevant antigen (pneumococcal polysaccharide) and to the nucleocapsid of RSV did not enhance infection. Blocking either the Fc segment of the monoclonal antibody of the Fc receptor on the cells diminished the enhancement, suggesting that this phenomenon involves attachment of the monoclonal antibody to the virus followed by attachment of the Fc of this complex to the Fc receptor on the cells. These data indicate that antibody-mediated enhancement of RSV infection can occur in vitro in macrophages. This enhancement may contribute to the pathogenesis of RSV bronchiolitis and the more severe RSV disease seen in recipients of formalin-inactivated RSV vaccine.