Twenty-four out of 25 patients with Chagas' heart disease have circulating immunoglobulins which react by indirect immunofluorescence technique with endocardium, interstitium and blood vessels of the heart. With skeletal muscle the reaction was observed in interstitium and vascular structures, but with other organs it was limited to vascular structures. This endocardial-vascular-interstitial factor (EVI) fixed complement. Some evidence indicated that this reaction could be obtained using the serum and tissues from the same patient: for instance, in one positive case a right atrium biopsy was performed. When this substrate was used for indirect immunofluorescence, employing the patient's own serum, positive results were obtained. Specificity is not related to AB blood group systems, or to Forssman or Wassermann antigens. The reacting factor was effectively absorbed from sera with organ homogenates, and with guinea pig red blood cells although it was independent of heterophil antibodies. In almost all cases studied, the EVI factor of the serum, when absorbed with epimastigotes ofT. cruzi, results in a negative reaction, suggesting that the genesis of the reacting gamma globulin is related to antigens ofT. cruzi.The EVI factor was also observed in 19 of 47 asymptomatic controls from an endemic area with positive serology forT. cruziand in 3 of 27 with negative serology. These 3 cases had anti-T. cruziantibodies in titers just below those considered of clinical value. The EVI factor was not observed in 119 normal individuals and 286 patients with selected cardiovascular diseases or another pathology from a nonendemic area. These findings and those mentioned above were statistically significant (P< 0.001). These results indicate the possibility of a more accurate diagnosis of chagasic myocardiopathy based on the study of the EVI factor, because in an individual case the diagnosis of chronic chagasic cardiopathy can be considered with a low probability in the absence of this factor.