SUMMARY Nineteen purebred Beagles of various ages (4, 5, 13, and 47 weeks) were inoculated with North American Trypanosoma cruzi isolates obtained from an opossum (Tc-O), an armadillo (Tc-A), or a dog (Tc-D). Dogs were grouped on the basis of clinical outcome of infection. During the acute stage of disease, dogs of group 1 (n = 7 inoculated with Tc-O or Tc-A) died or were euthanatized because of the severity of disease. Dogs of group 2 (n = 5 inoculated with Tc-O or Tc-A) developed acute disease, but survived to develop chronic disease. Dogs of group 3 (n = 7 Tc-Dinoculated dogs) developed neither acute nor chronic disease. Dogs of group 4 (n = 4—2 dogs 13 weeks old and 2 dogs 47 weeks old) served as noninoculated controls. Clinical signs associated with severe acute myocarditis developed in dogs of groups 1 and 2 between postinoculation day (pid) 15 and 28. Generalized lymphadenopathy and lymphocytosis were observed in all dogs of groups 1, 2, and 3 between pid 14 and 17. Serum alanine transaminase and aspartate transaminase activities and urea nitrogen concentration were high, and glucose concentration was low prior to death of dogs in group 1. Serum activities of isoenzymes of creatine kinase were significantly (P < 0.05) high in only 1 dog (group 1), whereas serum lactate dehydrogenase isoenzyme activities were not significantly high in any dog. Parasitemia was detected by examination of thick blood smears as early as pid 3, peaked by pid 17 in most dogs, and was not detected by pid 33 in dogs of groups 1 and 2. Parasitemia was documented by blood culture results in dogs of groups 2 and 3 at various times throughout the study. Dogs infected at an older age generally had lesser degree of parasitemia and higher survival rate than did dogs infected at a younger age. Dogs of group 2 did not manifest clinical signs of disease for 27 to 120 days prior to onset of chronic disease. Ventricular-based arrhythmias and exercise intolerance developed in all dogs of group 2 at various times by pid 120. Two dogs developed signs of biventricular heart failure.