1. Fifty-nine cases of megaloblastic anemia refractory partially or completely to potent liver extracts given parenterally have been investigated in Edinburgh during the past six years. Thirty-four of these cases were associated with pregnancy, the puerperium or the sprue syndrome. No explanation of the cause of the megaloblastic anemia was discovered in the remaining 25 cases.

2. The etiology, clinical features and treatment of 25 cases of idiopathic refractory megaloblastic anemia are described. Attention is directed to the excellent therapeutic effects produced by proteolysed liver or folic acid.

3. The mechanisms involved in refractoriness to potent parenteral liver extracts are discussed.

4. In certain cases of refractory megaloblastic anemia it is suggested that an unknown hematinic principle, in addition to the liberating factor in purified parenteral liver extract and folic acid, is required for the complete restoration of normoblastic blood formation.

ACKNOWLEDGMENTS My thanks are due to many members of my staff who have helped in these investigations, particularly to Professor L. J. Davis formerly lecturer in Medicine in the University of Edinburgh, and to Dr. Girdwood. Grateful acknowledgment must also be made to Doctor Riding, Medical Director of Evans Medical Supplies Ltd. and his research chemists who were responsible for the preparation of proteolysed liver and the other fractions of liver mentioned above.

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