This study was performed to establish whether signal-averaged electrocardiography can aid in the diagnosis of the familial form of arrhythmogenic right ventricular cardiomyopathy in order to determine the severity of the disease and to predict ventricular arrhythmias. In arrhythmogenic right ventricular cardiomyopathy there is a fatty fibrous substitution of myocardium, which is the substrate for delayed myocardial activation; this is responsible for the abnormalities seen on the signal-averaged electrocardiogram (SAECG). Seventy-five members of 11 families, both healthy and with various forms of the disease, were studied using a signal-averaged electrocardiographic technique. Forty-seven members, 16 with a severe and 31 with a minor form of the disease, were found to be affected. Forty-three subjects had abnormal results on the SAECG; of these, 39 had the disease (100% in patients with widespread disease and 74.1% in patients with a minor form), whereas the other 4 had no sign of the disease. Only 44.1% of the subjects with an abnormal SAECG had ventricular arrhythmias, whereas 76% of the subjects with ventricular arrhythmias had an abnormal SAECG. In contrast, 90.6% of patients with an abnormal SAECG had the disease, and only subjects with arrhythmogenic right ventricular cardiomyopathy had ventricular arrhythmias. The abnormality on the SAECG appears to be correlated with the severity of the disease. Signal-averaged electrocardiography does not seem useful in diagnosing the minor forms of the disease and it does not give precise information about electrical instability in these patients.