Gonorrhea was described in ancient Chinese, Japanese, Egyptian, Greek and Roman literature as well as in the scriptures of the Old Testament. The etiologic agent, a gram-negative bacterium-- Neisseria gonorrhoeae, is an obligate pathogen of humans. In the process of evolution, the organism has devised a very successful life style with respect to its human host. Infected humans do not develop an effective immune response to this pathogen, consequently silent, serial, and chronic infections are common. Our ultimate aim is to interfere successfully at some early stage of the disease process; in order to approach this problem, we must consider the biology of the host-parasite relationship. The surface of the gram-negative bacterium, the outer membrane, is a mosaic of tightly associated lipopolysaccharide (LPS) and protein molecules. Additionally, in some organisms, the outer membrane itself is covered by loosely bound polymers which comprise the bacterial capsule. It is the surface of the bacterium which interacts with the host in early stages of parasitism, and it is the host defenses against components of the bacterial surface which play a role in the prevention, resolution or, occasionally, exacerbation of bacterial diseases. We are engaged in the study of the structure and function of nonprotein surface constituents of N. gonorrhoeae. Those neisserial components of particular interest are the common proteolipid (the H.8 antigen), LPS, and the capsular polysaccharide. Our objectives are to isolate and characterize these surface molecules as well as the corresponding structural and regulatory genes in order to determine their role in the pathogenesis of disease.