Work in the Rickettsial Diseases Section has, for the last several years, focused on the structure and immunobiology of Rickettsia rickettsii, the etiologic agent of Rocky Mountain spotted fever, and related species with that genus. Major surface antigens of approximately 120 and 155 kDa have been identified. Monoclonal antibodies to these major surface proteins have been produced and used to characterize the antigenic diversity of the homologous proteins from distinct geographic isolates of R. rickettsii and closely related species. Certain of these monoclonal antibodies recognize critical surface structures and neutralize rickettsial infectivity. The potential of the 155 kDa protein as a protective immunogen has been further demonstrated by the protection of experimental animals from Rocky Mountain spotted fever by immunization with a cloned rickettsial gene product. Isolation and expression of the homologous gene from R. conorii, the agent of Mediterranean spotted fever, confirmed the potential of that protein as an immunogen since it induced protective immunity to R. conorii and to a lesser degree, protected against challenge with R. rickettsii. The monoclonal antibody data indicate that the 155 kDa antigen possesses both shared (genus-specific) and unique (species or strain-specific) antigenic determinants. Molecular characterization of these epitopes and their roles in protective immunity, species variation, and potentially virulence, is continuing. A limiting factor in these studies is the small amount of rickettsial gene product produced by the recombinant bacteria. In attempts to circumvent this difficulty, rickettsial gene promoters are being identified and alternative hosts for the expression of rickettsial genes are being explored. In addition, a gene expressing the 120 kDa antigen has been cloned and its sequence determined. Surface exposure, regulation of expression, and antigenic diversity of this prominent protein are being similarly characterized.