This is a continuing long-range study of the effects of purine antimetabolites on tumor cells and various normal tissues. Much of our current work involves the enzyme, adenosine deaminase (ADA), and its effect on a variety of adenosine analogs, as well as its interaction with the tight-binding inhibitor, deoxycoformycin (dCF). Current studies involve the role of cellular membranes in the mechanism of action of dCF and indicate that the nucleoside transport system is directly involved in delivery of the inhibitor into cells. Furthermore, when ADA is inhibited by dCF in erythrocytes, little reactivation of the enzyme occurs unless cells are hemolyzed. Studies continue on the potentiation of analog adenosine incorporation into nucleotides of cells incubated with dCF. Also, marked potentiation of the inhibition of the intracellular PRPP levels is produced when certain adenosine analogs are incubated with cells pretreated with dCF. Investigations on various adenosine analogs on blood platelets continue with special emphasis on the mechanism of inhibition of aggregation by agents such as ADP, arachidonic acid, thrombin, etc. Collaborative studies with the group of Professor Leroy Townsend continue, which makes available to our laboratory many novel purine nucleoside analogs for study in our biochemical systems.