An anemia with a positive direct and indirect Coombs' test was induced in Wistar strain rats by injection of the dye trypan blue. The anemia was characterized by a shortened red cell survival time, increased osmotic fragility and reticulocytosis. There was an associated leukopenia and thrombocytopenia. The positive Coombs' tests were regarded as a nonimmunologic phenomena and attributed to the protein binding properties of the dye. Splenomegaly and lymphadenopathy were constant findings in the anemic animals. Splenectomy did not alter the course of the anemia. The pathway of erythrocyte destruction was thought to involve the sequestration and destruction of protein coated cells in the spleen, lymph nodes and liver.