The importance of the Frank-Starling mechanism was evaluated in seven chronically instrumented fetal lambs (128-141 days gestation). Continuous determinations of left ventricular (LV) internal dimensions and pressures were obtained while LV end-diastolic diameter (LVEDD) was reduced by superior vena cava occlusion and increased by infusion of fetal blood into left atrium. A highly significant relationship was found to exist between stroke volume and LV extent of shortening (delta D) (r = + 0.99, P less than 0.001). Altering LVEDD from 10,5 to 13mm or LV end-diastolic pressure from 2.5 to 8 mmHg resulted in a 68% augmentation, in delta D. Spontaneous respiratory efforts resulted in frequent beat-to-beat variations in LVEDD and delta D, which maintained cardiac output constant over a wide range of respiratory rates. Moreover, LV output determined by indicator-dilution techniques remained unchanged over a wide range of spontaneous heart rates (114-180 beats/min) as a result of changes in delta D appropriate to alterations in LVEDD. Thus, changes in resting myocardial fiber length are of fundamental importance in fetal cardiovascular homeostasis and, within physiologic limits, it is quite clear that the Frank-Starling mechanism is operative and effective in the fetal lamb;