Mice immunized intramuscularly with a low dose, viable inoculum of C. psittaci survived an otherwise lethal intraperitoneal challenge with the homologous chlamydial strain. Immunized animals were not protected from intraperitoneal challenge by the unrelated pathogen, Listeria monocytogenes. Spleen cells from animals that exhibited protective immunity were suppressed in their proliferative responses to mitogens or chlamydial antigen in an in vitro blastogenic assay. This suppression was transferable to normal spleen cells by adding irradiated cells from immunized animals to normal cell populations. The degree of normal cell blastogenic suppression was dependent on the ratio of irradiated immune to normal cells present in the assay medium. Suppression of humoral responses was demonstrated in vivo. Immunized animals were incapable of producing antibody secreting cells to sheep red blood cells after an intraperitoneal inoculation of SRBC. Unimmunized animals produced a significant number of plaque forming cells as measured by a direct plaque forming cell assay. Lymphokine activity was not impaired in spleen cells from mice that exhibited other manifestations of suppression. Taken together, these data provide evidence to indicate that the induction of suppression may not correlate with increased pathogenesis, but rather be closely associated with protective immunity. Data also provide circumstantial evidence to indicate that lymphokine induction may be important in the development of protective immunity to C. psittaci in the mouse.