We have previously shown that a Pasteurella multocida cexA mutant (PBA875) was impaired in capsule export and highly attenuated in virulence for mice (J. D. Boyce and B. Adler, Infect. Immun. 68:3463-3468, 2000). In this study we show that immunization with high, but not low, doses of PBA875 can confer significant protection against wild-type challenge. We have also constructed a genetically defined acapsular P. multocida strain (AL18) by inactivation of bcbH, a gene predicted to be involved in polysaccharide biosynthesis. AL18 failed to produce immunoreactive polysaccharide as determined by immunofluorescence and Western immunoblot. Immunization of mice with live AL18 conferred significant protection against wild-type challenge, while immunization with similar doses of either killed wild-type or killed AL18 failed to confer protection.