Selected serum-mediated host immune defense mechanisms against Pasteurella haemolytica were studied using encapsulated and decapsulated organisms. When the capsular material was removed from P. haemolytica, it became more susceptible to serum agglutination, complement-mediated serum killing, and phagocytosis by polymorphonuclear leukocytes. When encapsulated organisms were used, phagocytosis was enhanced by antibodies to capsular material produced by vaccination of calves with any of three P. haemolytica vaccines. The serum bactericidal activity, however, was not facilitated by increased levels of anticapsular antibody in vaccinated cattle. By contrast, when decapsulated organisms were used, vaccination enhanced both the bactericidal and opsonizing capacities of sera from the calves. These studies indicate that capsular material should be considered a principal virulence factor for P. haemolytica.