Signal-averaged electrocardiography (ECG) was performed in 38 patients (mean age 38 years, range 15 to 70) with ventricular tachycardia who had no clinical evidence of structural heart disease. Spontaneous ventricular tachycardia was nonsustained in 23 patients and sustained in 15. None of the patients had symptoms of heart failure or ischemic heart disease, and at cardiac catheterization none had significant coronary artery disease or left ventricular wall motion abnormalities. In addition, all patients underwent left and right ventricular endomyocardial biopsy and ventricular stimulation studies. Signal-averaged ECG was performed and late QRS potentials were defined with use of Simson's method. Late QRS potentials were detected in a minority (18%) of patients including 2 of 23 with nonsustained and 5 of 15 with sustained (p = NS) ventricular tachycardia. Fifteen patients (40%) had abnormal endomyocardial biopsy results and these findings were more common in patients with sustained than in those with nonsustained ventricular tachycardia (9 of 15 versus 6 of 23, p less than 0.05). Late potentials were associated with abnormal endomyocardial biopsy findings (6 of 15 versus 1 of 23, p less than 0.01). An increase in fibrous tissue was the most frequent histopathologic abnormality; this increase was quantified by morphometric methods and compared with biopsy findings in normal control subjects. In the control group the proportion of collagen in relation to myocytes was less than 10%. All patients with both late potentials and abnormal biopsy findings had a greater than 15% ratio of collagen to myocytes in at least one specimen and the biopsies revealed marked interstitial fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)