Substituted purines were tested for their effectiveness in inhibiting the delayed hypersensitivity skin reaction (DHSR) caused by tuberculin in the guinea-pig. Among the tested purines were naturally occurring derivatives of guanine and adenine, including cyclic AMP. Based on the structure-activity profile, a class of purines was identified, the members of which were very effective inhibitors of inflammatory aspects of the DHSR and are characterized by a benzyl group in position 9, an amino or alkylamino group in position 6, and various substituents in position 2. This class of 2-substituted-9-benzyladenines was more effective in the DHSR than some antimetabolites, particularly the structurally related mercaptopurines.