Studies were performed on the reconstitution of the immune response to Shigella paradysenteriae and sheep erythrocytes in sublethally irradiated mice by the injection of normal peritoneal macrophages with and without pre-incubation with antigen. The response to Shigella was found to be less radiosensitive than the anti-SRBC response. Sublethally irradiated mice (550 r) injected with peritoneal macrophages from normal donors pre-incubated with Shigella antigen or injected simultaneously with macrophages and Shigella evinced a strong anti-Shigella response. No such reconstitution of the immune response against SRBC was observed, even when lower irradiation doses and phagocytosis-enhancing incubation media were used. Possible reasons for the different response to Shigella and SRBC are discussed.