It is crystal clear from the experiments tabulated below, in the accompanying Paper I, and elsewhere reported (3, 4) that the doubly depleted dog (anemic and hypoproteinemic) can use the growth mixture of ten essential amino acids to form large amounts of new blood proteins (hemoglobin and plasma protein), to maintain a positive balance between nitrogen intake and urinary nitrogen output, and to continue a healthy state for 3 to 6 weeks. Weight loss, regardless of the amounts of amino acids given by mouth or parenterally, ispractically always present and at times approaches or even exceeds the weight loss observed with zero protein intake.When the amino acid mixture is replaced by comparable amounts of good diet protein (estimated as nitrogen equivalents) we note an improved urinary nitrogen conservation, usually a decrease in new bIood proteins produced but a tendency to gain weight on a protein intake of 150 to 250 gin. protein per week. Given a suitable intake of a good food protein plus the basal protein-free diet, the dog will remain in a satisfactory state of double depletion for months with no weight loss and a liberal output of new blood proteins. Evidently the whole protein (egg, liver, meat, casein, lactalbumin) may contain something not found in the amino acid mixtures, as all other factors appear to be alike in the experiments. This missing substance or compound we assume is responsible for the increased conservation of nitrogen and weight gain. It appears probable that this type of experiment (double depletion) with anemia and hypoproteinemia places a severe strain on the animal--more than simple weight maintenance and of a different order than growth requirements. This severe test of double depletion may magnify the deficiencies of any amino acid mixtures or digests when compared with the best food proteins. The pattern of blood protein production in certain experiments is modified by these same factors (amino acids contrasting with food protein). Whatever this unknown substance may be, it is important to learn more about it. Eventually it should be of great value in the construction of amino acid mixtures and digests suitable for long continued optimum parenteral feeding.