Protective antigen (PA), the major protective component of the existing vaccine, is a potent immunogen. Protective antigen in alhydrogel induced a high serum IgG titre (> log10 4) in both the C57B16 and Balb/c mouse and the predominant subclass of antibody induced was IgG1, indicating that the response to PA was predominantly Th2 directed. When plasmid DNA encoding PA was used to immunize the Balb/c mouse, a low serum IgG titre was detected (</=log10 1), which was slightly increased by boosting with plasmid DNA. However, when mice immunized with plasmid DNA were later boosted with rPA, a significant and rapid increase in titre (up to threefold) was observed. Priming mice with PA-encoding plasmid DNA may be a mechanism of enhancing and accelerating the immune response to PA.