Studies were made on the ability of Xenopus laevis, the South African clawed toad, to produce an immunologic response to heterologous erythrocytes. Using tissue culture procedures, it was shown that spleen explants obtained from adult Xenopus can produce specific agglutinins and hemolysins when exposed to sheep or mouse red blood cells in vitro. Using a plaque-forming cell assay, it was demonstrated that the response in vitro is essentially similar to that obtained upon immunization in vivo, and that the response in both instances appears to be characteristically a primary one.