Neutralization of influenza virus is dependent on the classical pathway of complement. (A) PR8 virus was incubated with various concentrations of serum (B6 mice), and the levels of viable virus remaining in the samples were determined by measuring growth, in 10-fold dilutions, on MDCK cells (log10 TCID50). (B) The contribution of complement to virus neutralization was determined by incubating PR8 virus with heat-inactivated (HI) normal serum. (C) The role of classical pathway complements in neutralizing influenza virus was measured by incubating PR8 virus with sera (30%) from B6, C3−/−, C4−/−, and C1q−/− mice. Representative results for two similar experiments are shown. The horizontal line indicates the level of stock PR8 virus used in the assay (0% serum).