Anaphylactic reactions after transfusion of a small amount of red cell compatible blood is described. Typical manifestations were substernal pain, dyspnea, and severe normovolemic shock. All the four patients lacked IgA and were found to have antibodies to IgA with titers from 500 to 16,000, as determined by a passive hemagglutination assay. In immunodiffusion against IgA, a single precipitation line was produced by three of the four serums. The antibodies were shown to be IgG by ultracentrifugation, gel filtration, immunoelectrophoresis, and ion exchange chromatography. The antigen-antibody complexes were able to fix complement. Lack of cell-bound immunity was suggested by the failure of IgA to stimulate lymphocytes from one patient. Two of the patients received IgA-deficient blood or plasma; both tolerated the transfusion without ill effects. Twice-washed erythrocytes from normal blood provoked a reaction in the third patient, but after three additional washings, no reaction was observed.