We have found that the enzyme Adenosine Deaminase (ADA) is absent in approximately 50% of patients with combined immunodeficiency (CID) (1). Parents of the affected children have been shown to be heterozygotes for the defect. The enzyme defect has been demonstrated in erythrocytes as well as in circulating lymphocytes. Complete absence of red cell ADA has so far not been demonstrated in any normal subject or any disease other than combined immunodeficiency syndrome. Deficiency of ADA appears to represent the first enzymatic derangement found in immune disorders. We propose to study the relation of ADA to lymphocyte function, its role in the nucleic acid metabolism of lymphocytes, the presence or absence of this enzyme in various human and animal tissues, the ontogenetic development of the enzyme in relation to the development of human lymphoid tissues and its familial transmission.