As an intracellular bacteria, Chlamydia trachomatis is an extraordinarily successful pathogen. Chlamydial infections are among the most common of all human infections. Chlamydial disease is less common than infection and is attributed to immune responses to specific antigens of the organism. A major variant surface protein, major outer membrane protein (MOMP), is the principal target of neutralizing antibodies and may be the target of protective immunity. The detailed genetic and immunochemical knowledge of MOMP has stimulated multiple attempts to design an oligopeptide vaccine. Success has been limited in part because of the antigenic variation that the protein exhibits and in part because of the absence of knowledge regarding the three-dimensional structure of the protein. Individuals with severe forms of chlamydial disease often display immune responses to a common chlamydial heat shock protein 60 (hsp60) antigen. Because the protein shares nearly 50% sequence identity with the human homolog, it is speculated that molecular mimacy may result in autoimmune inflammatory damage that in turn causes chlamydial disease sequelae. Because hsp60 immune responses are genetically determined, susceptibility genes for chlamydial disease may also exist. A detailed understanding of the immunobiology of C. trachomatis infection may result from molecular study of chlamydial antigens and the precise nature of immune responses they elicit. Nevertheless, even with the rapid progress that has been made in uncovering the major chlamydial antigens, more remains hidden than revealed. As demonstrated by their successful ecology, chlamydiae remain several stops ahead of even their most ardent pursuers.