1. 1. Large differences were found in activities and kinetics of adenosine and deoxyadenosine metabolizing enzymes in lymphocytes and erythrocytes of man and various mammalian species. 2. 2. ADA and PNP activities in erythrocytes do not always correlate with those in lymphocytes of the same species. 3. 3. ADA activity was low in equine and porcine lymphocytes, PNP activity was low in ovine and caprine lymphocytes. Adenosine and deoxyadenosine showed comparable K m values for ADA in lymphocytes of man, horse and pig; in equine lymphocytes these values were lower. 4. 4. Purine 5′-nucleotidase activity was low in lysates of lymphocytes of horse and pig, intermediate in those of sheep and high in those of man. The same pattern was found for ecto-S′-nucleotidase. 5. 5. Adenosine was phosphorylated at a higher rate than deoxyadenosine in lymphocyte extracts of man, horse and pig. Activities are comparable in all species. The K m value of adenosine for adenosine kinase is higher but the K m value of deoxyadenosine for phosphorylation is lower in human lymphocytes than in lymphocytes of horse and pig. Deoxycytidine markedly inhibited deoxyadenosine phosphoryla- tion in human lymphocytes and to a lower extent in equine and porcine lymphocytes. Adenosine considerably inhibited deoxyadenosine phosphorylation in lymphocytes of horse and pig, while it had no effect in human lymphocytes. 6. 6. Activity of S-adenosyl-homocysteine hydrolase, measured in the synthetic direction, was lower in human lymphocytes than in those of pig and horse. Deoxyadenosine markedly inhibited enzyme activity only if it was preincubated with the enzyme without adenosine. 7. 7. The observed differences in adenosine and deoxyadenosine metabolism between human lymphocytes and those of horse and pig may explain why equine and porcine lymphocytes show a normal immune function despite a low ADA activity.