The paralysing effect of brief exposure to antigen has been studied in a system in which cells were exposed and then tested by challenge immunization after transfer into syngeneic unresponsive mice. Bovine and human serum albumins (BSA and HSA) were used chiefly, but lysozyme was also tested. Irradiation and paralysis on their own had drawbacks as methods of procuring unresponsive hosts, and worked best in combination. The response measured in the hosts as antigen binding capacity (ABC) was found to be proportional to the number of reactive cells transferred. Lymph node cells and blood leucocytes proved more active than spleen cells. Cells did not become paralysed immediately upon exposure to high concentrations of antigen; blood leucocytes required approximately 2 hours in vivo exposure, and cells from lymphoid organs approximately 24 hours. The effectiveness of 24 hours exposure depended on antigen dose. Tentative measurements of the time taken for antigen to diffuse through the organs suggested that this delay would not account for the difference in timing between cells of different anatomical origin. Exposure in vitro was not found repeatably effective in inducing paralysis. The conclusion was drawn that paralysis is induced by the direct action of antigen on lymphocytes, but that the cells may undergo some further step of differentiation before induction is complete.