Four monoclonal antibodies (mAbs) recognizing distinct antigenic sites on the HA2 glycopolypeptide of influenza virus A/Dunedin/4/73 (H3N2) have been tested for in vivo protection. When applied intravenously before infection, three of them increased the survival of BALB/c mice infected with 1 LD(50) homologous virus. The protection resulted simultaneously in 2 days earlier clearance of virus from the lungs. These three antibodies inhibited the fusion activity of virus in previous in vitro experiments. One of them, specific to N-terminal aa 1-38 of the HA2 glycopolypeptide, was also tested for protection against the heterologous virus A/Mississippi/1/85 (H3N2). Protection similar to that against the homologous virus was observed. The fourth mAb, without fusion-inhibition activity, did not protect mice. It is concluded that antibodies specific to the antigenically conserved HA2 glycopolypeptide that exhibit fusion-inhibition activity can contribute to the protection of infected mice and mediate more effective recovery from infection.