Explants of rabbit spleen, responding to sheep erythrocytes in vitro, were exposed to ionizing radiation at different times in culture. Radiation was found to depress the development of specific haemolysin-producing cells (PFC) at subsequent times, while cells already engaged in haemolysin production were relatively resistant to radiation. The depressing effects of radiation on PFC was most marked at times when the rate of increase of PFC was highest. Recovery from low doses (less than 2 Gy) occurred while higher doses of radiation had persistent depressing effects on the level of PFC. Assessment of synthesis of other macromolecules in these irradiated cultures showed that protein synthesis was highly resistant and DNA synthesis was sensitive like the immune response. Irradiation in hypoxic conditions showed that this protected the tissues from damage by radiation and there were also indications of enhancement of repair of this damage. Finally it was found that the results obtained with these cultures correlated well with previous studies of intact mice.