The virulence and the adherence to porcine respiratory tract cells and mucus of three toxigenic, capsular type D Pasteurella multocida isolates and their noncapsulated variants were evaluated in the present study. Loss of capsule by P. multocida, verified by transmission electron microscopy after polycationic ferritin labeling, was associated with a massive reduction in virulence of the organisms in mice. Specific-pathogen-free piglets inoculated intranasally with one of the capsulated isolates or its noncapsulated variant developed turbinate lesions characterized by bone resorption and by an inflammation of the mucosa associated with hyperplasia and squamous metaplasia of the epithelium. Infection with the capsulated isolate led to more severe lesions and atrophy of turbinates. The interactions of these P. multocida isolates with porcine respiratory tract cells and mucus were studied in vitro. The presence of capsule resulted in a decrease in binding of respiratory tract mucus were studied in vitro. The presence of capsule resulted in a decrease in binding of respiratory tract mucus to P. multocida isolates as determined by a dot blot assay. The presence of capsule also resulted in a significant decrease in adherence to porcine tracheal rings maintained in culture. The capsule seemed to mask outer membrane components which are involved in adherence. One of these components might be lipopolysaccharide since purified lipopolysaccharide bound respiratory tract mucus and blocked adherence of this microorganism to porcine tracheal rings. Our data indicate that capsular material does not seem to be involved in adherence of P. multocida to respiratory tract cells and mucus, but capsulated isolates are more virulent in mice and also in piglets.