Recent clinical studies of pulmonary embolism indicate that typical ECG changes of acute right ventricular overload become evident only with severe pulmonary hypertension. The present study was performed to determine whether less obvious yet consistent ECG changes are present during mild and moderate pulmonary hypertension and to what extent hypoxia modifies the ECG response. Three series of experiments were performed; each employed 6 dogs. The orthogonal ECG (McFee system) was recorded at 3 levels of pulmonary artery (PA) mean pressures: control, 20 and 40 mm Hg in closed-chest dogs with and without hypoxia. Mean arterial pO2 was 53 mm Hg in the hypoxic series. Pulmonary hypertension was induced by means of a PA balloon catheter. Right ventricular (RV) volumes were determined from biplane cineangiograms in a separate series. The ECG analysis was performed utilizing digital computer techniques. No significant ECG changes were produced by a mean PA pressure of 20 mm Hg despite a 17% increase in RV end-diastolic volume above control values. At 40 mm Hg and a 45% increase in RV volume, dogs in the series without hypoxia showed a small but significant posterior shift of the initial QRS vector. Hypoxic dogs demonstrated directionally similar but more prominent changes with significant posterior displacement of both early and late QRS vectors and posterior-superior ST displacement. Thus, this study confirmed clinical data suggesting that the ECG is an insensitive indicator of acute RV pressure overload. ECG changes present at high PA pressures were accentuated by hypoxia.