Interventricular septal involvement in myocardial infarction is suggested by the findings of a QS deflection in lead V1 and/or absence of the Q wave in leads I and V6, using the standard 12-lead electrocardiogram (ECG). However, these findings were not sufficiently established for the criteria of septal infarction, because several factors including anatomic position of the heart, changes of intraventricular conduction, and condition of the lung would affect the QRS complex in the leads. In this study, we analyzed the ECGs of anterior myocardial infarction with (group A) and without (group B) involvement of the first septal coronary artery. The R wave in V1 was absent in 64.7% of group A and 60.0% of group B. The Q wave was absent in 35.3% in lead I and 64.7% in lead V6 of group A, while in group B the Q wave in leads I and V6 were not observed in 60.0% and 40.0%, respectively. The prevalence rates of the R wave and the Q wave in these leads were not significantly different between the two groups. Left ventriculography revealed that the prevalence rate of the R wave in V1, and the Q wave in I and V6 was not significantly different, regardless of the presence or absence of impaired septal motion. Experimental study in anesthetized dogs confirmed the difficulty in clarifying acute septal ischemia by changes in the QRS complex. These results indicate that septal myocardial infarction is hardly detectable with changes in the QRS complex of the standard 12-lead electrocardiogram.