Rats were fed a basal diet supplemented with (2.57%) 3-methylthiopropionate (MTP) for 2 weeks. A marked depression in growth and food intake similar to that found in rats fed an equimolar level of methionine was observed. While supplemental glycine or serine alleviated the toxicity due to dietary methionine, similar levels added to the diets of rats fed MTP were without effect. The spleens of rats fed diets containing 2.57% MTP were grossly enlarged and darkened in comparison to spleens from control rats and histological examination of these spleens by light and transmission electron microscopy (TEM) revealed sequestration of large numbers of erythrocytes in the splenic sinusoids and red pulp similar to that seen in rats fed high levels of methionine. Marrow changes included increased numbers of erythroblastic islets and subtantial electron dense hemosiderin deposits in islet reticulum cells. Examination of peripheral blood erythrocytes by scanning electron microscopy revealed extensive variation in the size of the erythrocytes and the presence of large numbers of misshapen red cells in rats fed the diets containing MT. When viewed by TEM many erythrocytes had obvious membrane defects and remnants of cytoplasmic organellae. Many erythrocytes with reticulocyte morphology were present in the peripheral blood. This condition is characteristic of maturation arrest at the reticulocyte stage of development. The similarity of depression in growth and food intake and the identical abnormalities found in the spleens of rats fed high levels of MTP and methionine suggest that the transamination pathway of methionine catabolism may be important with respect to the toxicity of methionine. The ultrastructural changes noted in MTP-fed rats suggest a serious dysfunction of red cell hematopoiesis. The large numbers of defective and/or immature erythrocytes released from the marrow into the peripheral circulation, only to be later sequestered and destroyed in the spleen, is a reflection of a serious derangement.