We have developed an ascorbic acid-dilution method for measuring cardiac output which requires minimal blood withdrawal. Ascorbate is injected into a central venous catheter. The indicator-dilution curve is obtained by drawing blood from an arterial catheter through an amperometric cell at 0.96 ml/min for 35 s. The current is measured by a picoammeter . A calibration curve is obtained in 15 s prior to each indicator-dilution curve. An on-line digital computer measures the curve areas and calculates the cardiac output. Cardiac outputs of heparinized dogs anesthetized with pentobarbital and halothane measured by this method (AA) compared closely to cardiac outputs measured by the dye-dilution method (CG) (AA = 0.96 CG + 20 ml/min, r = 0.98). Both the cardiac output and the arterial blood pressure remained stable during replicate measurements of the cardiac output of 1-day-old piglets. This system allows cardiac output determinations of neonatal subjects without excessive blood removal and, with further development, should be practical in human neonates.