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To determine whether the hyperkinetic circulatory response to chronic anemia is obligatory and to assess its strength and potential reversibility, the hemodynamic state at rest was assessed (indicator-dilution method) in 24 patients with chronic anemia before and after certain interventions. A comparison of cardiac output measured before and after treatment established the consistency of the hyperdynamic response to anemia. In the absence of convalescent data, this response might have been overlooked in some anemic patients whose cardiac output fell within the normal range. In the anemic state, cardiac output correlated negatively and significantly with age (r=-0.752). This relationship may account for the apparent absence of the hyperkinetic circulation in elderly, anemic patients. In only the most anemic (hemoglobin, 3.8 g/100 ml) of six patients did inhalation of 100% oxygen lower cardiac output significantly. In four patients, studied in both the supine and sitting posture, orthostatic stress was consistently accompanied by a decrease in central blood volume (7%) and an increase in total systemic resistance (64%), resulting in a reduction of both stroke index (28%) and cardiac index (23%). Administration of methoxamine to seven anemic patients resulted in increases in mean arterial blood pressure (24%) and total systemic resistance (40%) in all and a decrease in cardiac output in all but one patient (mean, 20%). Peripheral vasoconstriction induced by means of orthostatic stress or by a pressor amine thus effected an acute reversal of the high output state in chronic anemia. These observations suggest that redistribution of blood volume and vasodilatation play a dominant role in the hyperkinetic circulatory response to chronic anemia and indicate that this state is labile rather than fixed.