With few exceptions, immunity from chlamydiosis availed by current vaccines is limited and can even be detrimental. Possible reasons for failure include immunotype or strain differences, ill-defined virulence variation, presentation of deleterious antigens, and incorrect presentation of critical antigens to the body. Antigens that stimulate neutralizing antibodies active at 2 steps of infection have been identified. A third step, prevention of phagolysosomal fusion, needs to be further studied, and causal antigens need to be identified. A fourth possible stage for antibody participation is in antibody-dependent cell-mediated cytotoxicity. If chlamydial antigens are expressed on the surface of infected cells, this mechanism of destruction of infected cells and the antigens that elicit it will need to be more fully examined. Cell-mediated immune responses participating in eliminating chlamydial infections need to be further clarified. Activated macrophages are the best characterized effector mechanism of cell-mediated immunity thus far, regardless of the stimulatory cytokines involved. It is important to determine how sensitized lymphocytes recognize antigen(s) that cause them to release macrophage-activating cytokines. It must be determined whether chlamydial antigens are expressed on the surface of infected cells and then recognized by potential cytokine-releasing lymphocytes in context with major histocompatibility antigens (surface expression) or whether they are recognized on antigen-presenting cells functioning in more of a scavenging capacity. Membrane expression of antigen is also important in that it also defines whether cytotoxic T cells and antibody-dependent cell-mediated cytotoxicity have roles in resistance to chlamydial infection. Also, it is important to realize the possible limitation of these mechanisms to systemic sites of the body. If membrane expression does occur, it must be determined how it functions at mucosal sites, whether it occurs at the luminal surface of mucosal epithelial cells only, or whether there is expression of antigens at abluminal membrane surfaces perhaps more accessible to such immune effector mechanisms. Delivery of critical antigens to the individual is the final component in establishing effective vaccines. Carrier systems capable of stimulating long-lasting mucosal and systemic immunity are available and need to be further studied as protective immunogens become available.