The effects of stepwise isovolemic hemodilution on systemic and regional hemodynamics, oxygen flux, and circulating catecholamines were studied in six pigs anesthetized with midazolam and fentanyl. Reduction of the hematocrit from 28 to 9% resulted in doubling of the cardiac output, mainly due to an increase in stroke volume. Regional blood flows, measured using the radioactive microsphere technique, showed an increase in blood flow to all organs except liver (hepatic artery fraction) and adrenals, with a redistribution of cardiac output in favor of heart and brain (increase in blood flow 420 and 170%, respectively). Oxygen flux to most organs did not decrease until hematocrit decreased to 9%, while total body oxygen consumption was well maintained. Left ventricular oxygen consumption increased, but because left ventricular blood flow also increased, left ventricular extraction ratio did not increase. Circulating catecholamines did not play any role in these regulatory mechanisms.