The functional status of the sympathetic nervous system in Chagas' heart disease is still the subject of intense controversy. To determine the nature of the abnormalities of the sympathetic nervous system, we measured the plasma norepinephrine concentration of chagasic patients with varying degrees of myocardial damage. Thirty-six patients with positive serology for Chagas' disease were studied. Twenty patients were in Functional Class I (New York Heart Association), 10 were in Functional Class II and six were in Functional Classes III-IV. Cardiac catheterization was performed in 24 patients. The asymptomatic patients had a plasma norepinephrine concentration (121 +/- 37 pg/ml, mean +/- S.D.) not different from normal controls (103 +/- 59 pg/ml). The symptomatic patients, however, had a significantly elevated plasma norepinephrine concentration (665 +/- 354 pg/ml, P < 0.001). The baseline heart rate of the asymptomatic and symptomatic patients directly correlated with the plasma norepinephrine concentration (r = 0.69, P < 0.0001). The symptomatic patients had larger ventricular volumes, higher left ventricular end-diastolic pressures and lower ejection fractions than the asymptomatic patients and normal controls. The plasma norepinephrine concentration correlated linearly with the left ventricular end-diastolic volume (r = 0.77, P < 0.0001), and non-linearly with the ejection fraction (r = -0.70, P < 0.0001) and the left ventricular end-diastolic pressure (r = 0.53, P < 0.007). These results indicate that, in Chagas' heart disease as in most other cardiac diseases, sympathetic nervous system activation is a late and compensatory phenomenon. In other words, sympathetic activation is very likely related to the progressive impairment of left ventricular function.