A negative U wave is highly specific for the presence of heart disease and is associated with other electrocardiographic abnormalities in more than 90 percent of patients. The three most common conditions associated with a negative U wave are systemic hypertension, aortic and mitral regurgitation and ischemic heart disease. The U wave vector is directed opposite to the QRS axis in the horizontal plane in patients with both left and right ventricular hypertrophy. In patients with ischemic heart disease, the U wave vector tends to be directed away from the site of the akinetic or dyskinetic region. The change from a negative to an upright U wave after a reduction in blood pressure, renal transplantation, insertion of a valve prosthesis or a coronary arterial bypass graft procedure is associated with a decrease in the QRS amplitude but with no consistent changes in T wave polarity. The timing of the U wave apex is dependent on the duration of ventricular repolarization but not on the duration of the QRS complex. This finding and other electrocardiographic observations are explained better by the ventricular relaxation than by the Purkinje fiber repolarization theory of U wave genesis.