It was postulated that the anemia commonly seen in mammalian trypanosomiasis, and specifically in Trypanosoma congolense-infected calves, was of immunological origin. Specifically, we postulated that trypanosome antigen-antibody-complement complexes, deposited on the surface of erythrocytes of infected calves, resulted in their immune elimination leading to clinical anemia. This hypothesis was tested experimentally. Immunoglobulins bound to the erythrocytes of 13 infected calves were detected by a direct antiglobulin test from 7 to 10 days post infection. The reaction was strongest between 3 and 9 weeks and remained inconsistently positive until the calves were killed by euthanasia 15 to 18 weeks after infection. Erythrocytes reacting positively in this test were then lysed and immunoglobulins were eluted from the washed stromata by means of a low pH buffer. Sixteen out of 74 eluates prepared in this way and concentrated, contained IgM and IgG. Antibody activity of these eluates against T. congolense was demonstrated by means of the complement fixation test, the indirect hemagglutination test, and the indirect antiglobulin test. It is considered that the original hypothesis has been essentially proven.