To investigate the role of complement (C) in the recovery from a primary viral infection in vivo, the course of influenza infection in decomplemented BALB/c mice and in C5-deficient B10.D2/OSN mice was examined. BALB/c male mice decomplemented with cobra venom factor demonstrated a prolonged viral infection, an increased degree of pulmonary consolidation, and a higher rate of morbidity and mortality than did nondecomplemented mice for each dose of virus administered. This deleterious effect occurred in mice decomplemented before infection and immunologic induction, as well as in mice decomplemented after infection and immunologic induction, provided the C3 levels remained depressed at the time of viral clearance (days 7 to 9). The time of appearance and the levels of serum neutralizing antibodies and viral-specific cytotoxic T cells were equivalent in decomplemented and nondecomplemented BALB/c mice infected with influenza. Similarly, C5-deficient B10.D2/OSN male mice, infected with influenza, demonstrated a prolonged viral infection, an increased degree of pulmonary consolidation and a higher rate of mortality than did C5-sufficient B10.D2/NSN agematched mice for each dose of virus administered. These results suggest than an intact complement pathway plays an adjunctive role in host recovery from primary influenza infection.