8-Azaguanine does not inhibit the growth of the Tulahuen strain of Trypanosoma cruzi in vivo, or produce any curative effects. Instead it produces an intensified infection in C3H mice when the dosage is 75 mg of 8-azaguanine/kg/day, which may be due to antibody suppression in the host by the drug. The parasitemias of the experimental animals were significantly greater than the controls, and eight tissues were significantly more parasitized. These tissues were: adrenal cortex, bone marrow, brown fat, colon, diaphragm, duodenum, pancreas, and spleen. It is interesting that the most heavily parasitized tissue, brown fat, and the adrenal cortex also contain the most steroids. Nakamura and James (1952) experimented with 10 purine derivatives, not including 8azaguanine, against Trypanosoma cruzi in vitro. They found that oxygen consumption and growth were inhibited by all of the derivatives studied. They indicated that further study of the effects of purine and pyrimidine derivatives on T. cruzi seemed desirable. Jaffe (1963), in experiments with Trypanosoma equiperdum, found that infected mice showed an 8% increase in survival time when treated with 20 mg 8-azaguanine/kg/day. From early experiments with 8-azaguanine on Tetrahymena geleii it was postulated that the protozoan substituted 8-azaguanine for the normal guanine and incorporated it into nucleic acids, with a resulting metabolic disturbance and growth failure (Kidder and Dewey, 1949). Since then the analog has been isolated from the RNA of 8azaguanine-inhibited cultures of Tetrahymena (Heinrich et al., 1952), and from the nucleic acids of tumors and viscera of mice treated with 8-azaguanine (Mitchell et al., 1950). 8-Azaguanine has been shown to be substituted for guanine in bacterial, viral, and mammalian RNA replacing up to 5% of the guanine residues (Lasnitzki, 1954). Smith and Matthews (1957) found that 40% of total RNA guanine in Bacillus cereus can be replaced, and Levin (1963) demonstrated that most of this 8azaguanine was incorporated into sRNA. Parks (1962) demonstrated that at daily dosages of 75 mg/kg the average survival time of mice with mammary adenocarcinoma was almost twice that of untreated control animals. In Received for publication 13 August 1968. general, investigations in many laboratories all point to inhibition of protein synthesis as an important or major effect of 8-azaguanine on tissues (Parks, loc. cit.). The 8-azaguanine inhibition of antibody synthesis was demonstrated by Dutton et al. (1958) in spleen cells of rabbits, and by Malmgren et al. (1952) who found reduced hemolytic and precipitin antibody titers in several strains of inbred mice. The present report deals with investigations designed to demonstrate effects of 8-azaguanine on the pathogenesis of acute experimental Chagas' disease. MATERIALS AND METHODS The Tulahuen strain of T. cruzi was the infective agent. The strain was virulent when sent to us by Dr. Frans C. Goble, Ciba Pharmaceutical Company, Summit, New Jersey, and remained virulent throughout the experiments. The trypanosomes were maintained in HM medium (Warren, 1960). Adult C.H mice (mean weight 23 g) were used and were maintained on a diet of Purina Laboratory Chow. The experiments (1 to 4) were run separately in the sequence in which they are presented. A total of four different tubes of medium (each containing 10 ml of fluid) were used, one tube for each experiment. Care was taken to insure equal distribution of the cycle stages to experimental and control mice in each experiment by using inocula from the same tube of medium. At the time of the inoculations the trypanosomes had been in culture 14 days. Special care was taken to prevent concomitant bacterial infections by examining the medium before use in each experiment and following aseptic techniques throughout all of the inoculations. Each animal was inoculated subcutaneously with 0.1 ml of medium containing a total of ca. 500,000 trypanosomes as counted with a hemocytometer counting chamber. Fourteen to 18% of the total trypanosomes counted were infective metacyclic stages making a total of 70,000 to 90,000