Extract: These studies have determined the erythropoietic response of the chronically calorie-deprived pig to the hypoxic stress of phlebotomy. Three animals were maintained on diets sufficiently restricted to prohibit weight gain from twenty-one days to six months of age. The animals were anemic, with hematocrit values of 35%, and were subjected to controlled phlebotomy of one-third the total erythrocyte mass. During a subsequent two-month period, two of the animals were given a caloric diet ad libitum and a seven-fold increase in weight, accompanied by active erythropoiesis and an increase in hematocrit, was observed. Phlebotomy studies were repeated after the period of ad libitum feeding. The erythropoietic response to phlebotomy was evaluated in both the undernourished and the rehabilitated pigs by study of erythropoietin excretion, circulating reticulocyte numbers, iron kinetics, Cr51 total RBG mass, bone marrow morphology, and changes in serum iron concentration. When measured on day 2 preceeding phlebotomy, the calorie-deprived animals had very low concentrations of urinary erythropoietin (0.06 U/24 h) which, following blood loss, promptly increased to a concentration of 2.0 U/24 h. A similar prompt response was seen in the rehabilitated animals (fig. 1). Prior to phlebotomy, plasma iron turnover was < 1.0mg/100 ml whole blood/24 h and promptly increased to 1.5–2.0 mg/100 ml whole blood/24 h by four days after phlebotomy (fig. 2). There was a marked increase in iron utilization for erythrocyte production when measured six days following phlebotomy (fig. 3). A decrease in the myeloid: erythroid ratio of the marrow accompanied these other evidences of increasing erythropoiesis (fig. 4). The degree of response in the calorie-deprived and in the rehabilitated animals was similar. The calorie-deprived animals had a higher reticulocyte response to phlebotomy than the animals fed ad libitum, but reestablished the prephlebotomy hematocrit no more rapidly (figs. 5 and 6). The higher reticulocyte counts in the undernourished pigs was shown to be related to less mature reticulocytes entering the circulation following the bleeding stress, reflecting a greater degree of marrow ‘shift’ (fig. 8). Calculation of total erythrocyte production in response to phlebotomy under conditions of severe caloric deprivation and ad libitum feeding demonstrates that a comparable response occurred under both experimental conditions. Speculation: These studies support the hypothesis that anemia accompanying chronic caloric deprivation in the pig is not caused by a primary lack of essential nutrients, but represents an adaptive response to the decreased metabolic needs of the chronically undernourished organism. It is likely that the moderate anemia sometimes seen in marasmic infants is due to a similar mechanism. If such is the case, therapeutic measures such as blood transfusions and administration of various hematinics directed primarily at altering this adaptive phenomenon would appear contraindicated in the management of the marasmic infant.