The effects of volume and pressure loading of the left ventricle on posterior wall thickness and left ventricular wall stress in transposition of the great arteries were studied by combining echocardiographic and cardiac catheterization data. Pure volume loading with low left ventricular pressure resulted in little or no thickening of the left ventricular posterior wall (0.52 mm/log month). Pressure loading to levels above half of the right ventricular pressure was associated with thickening (2.80 to 3.89 mm/log month); however, further increase in pressure or volume load did not significantly alter the rate of thickening. Estimates of ventricular wall stress using a simple radius/wall thickness ratio may be misleading. However, if allowance is made for variable ventricular geometry and pressure, estimated wall stress is constant in transposition and is approximately equal to that reported previously in patients with normally related great arteries. The walls of low-pressure left ventricles in patients with transposition are demonstrably thinner than those of high-pressure left ventricles by age 1 to 3 months (2.67 versus 3.52 mm). Surgical procedures to use the left ventricle for systemic work, such as the arterial switch operation, should be performed in the first month of extrauterine life. Preparatory operations, if necessary prior to arterial switch, should load the left ventricle to greater than half systemic pressure.