The purposes of the present studies are to define the conditions for a satisfactory in vitro model for immunity to pneumococcal polysaccharide (SIII) in mice, to analyze the cellular requirements for this response, and to characterize the cells and/or factors which can augment or suppress that response. Significant reproducible IgM and IgG anti-SIII plaque-forming cell (PFC) responses have been obtained from normal BALB/c spleen cell suspensions cultured for 4-5 days in Mishell-Dutton cultures with small amounts of SIII (optimal 5x10 to the minus 6th power micron/ml). Cells from mice previously primed in vivo with 5x10 to the minus 3rd power micron SIII were specifically unresponsive when re-exposed to an optimal amount (for normal cells) of the same antigen in vitro. Furthermore, small numbers of SIII-primed spleen cells were able to specifically suppress the anti-SIII PFC response of normal cells to the otherwise optimal dose of SIII in vitro. These results indicate that the unresponsiveness to SIII induced by pre-exposure to antigen is an active process. Studies are underway to characterize the cells and/or factors responsible to this suppression.