The primary goal of this proposed research is to develop an understanding of the syphilitic disease process. This research will focus on two central questions--How does the organism cause disease? and How does the host respond to eradicate the disease? Not much is known about either the pathogenesis of Treponema pallidum or the subsequent host responses that produce immunity. A number of important observations have emanated from the previous four years of research in these two areas. This proposed research will attempt to solidly confirm and extend previous work involving the mucopolysaccharide capsule of T. pallidum and the mucopolysaccharidase enzyme of T. pallidum. Pathogenesis and immunity will be compared using strains of T. pallidum which exhibit a varied spectrum of virulence, ranging from the highly virulent Chicago strain to the less virulent strain H. Comparisons will also be made to non-pathogenic treponemes and to other pathogenic treponemes such as T pertenue, T. carateum, and T. paraluiscuniculi. Four separate areas will be investigated: in vitro aspects of treponemal and host mucopolysaccharides, in vivo aspects of treponemal and host mucopolysaccharides, in vitro aspects of treponemal host mucopolysaccharides, in vitro aspects of treponemal mucopolysaccharidase, and in vivo aspects of treponemal mucopolysaccharidase.