Recent interest in the use of the purine antimetabolites in the treatment of diseases of proved or postulated immune etiology prompted a study of the effect of 6-mercaptopurine (6MP) on antibody formation in atopic individuals. Six prison inmate volunteers with ragweed hay fever and/or asthma (treatment group) were matched according to age, sex, and race with six ragweed sensitive patients who served as untreated controls. Subjects in the treatment group were given 6MP, 1.5 mg. per kilogram per day by mouth for 21 to 42 days. As compared with the control group, subjects in the treatment group demonstrated the following: diminished antibody response following immunization with E. coli Vi antigen; no change in pre-existing titers of ragweed reagin as measured by direct skin test and passive transfer studies; no change in pre-existing hemagglutinin titers to diphtheria toxoid; and no change in pre-existing serum concentration of gamma-1A, gamma-1M, or gamma-2 globulin. Two subjects in the treatment group developed toxicity which necessitated discontinuance of the drug. Bone marrow examinations at the end of the study revealed macronormoblasts in four treated patients. The lack of suppression of pre-existing antibody titers, including reagin, suggests that when used under the conditions studied, and aside from possible nonimmunologic effects, 6MP would be of little value in treatment of the atopic diseases.