Grossly enlarged spleens are always present in guinea pigs made anemic by cholesterol feeding. Other indications of the hemolytic nature of this anemia are hyperplastic bone marrow, increased fragility of erythrocytes, fatty livers and high serum bilirubin. In a group of 15 splenectomized guinea pigs, 2 were fed a grain stock diet, 6 a "basal" diet containing 20% casein, 10% yeast, and 12. 5% fat, and 7 were given this "basal" diet plus 1% cholesterol. The splenectomized animals given the stock diet appeared normal. Tolerance for the "basal" diet was somewhat lessened by splenectomy. Growth was poor and there were some indications of a red cell destruction slightly greater than normal. Splenectomized animals given the basal diet with 1 % cholesterol had erythrocyte counts which fell to approx. 3 million in 50-60 days. Livers were markedly fatty and serum bilirubin was high. Anemias were fully as severe as in the intact animals on the same diet. This would indicate that the enlargement of the spleen does not produce, nor does its removal prevent, the anemia of cholesterol-fed guinea pigs.