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In this study, the cardiac output of 11 children (5 days to 18 yr of age) was measured following cardiopulmonary bypass. Standard dye dilution cardiac outputs and an indirect Fick-CO2 technique were simultaneously determined. A rebreathing maneuver is described to estimate the oxygenated mixed venous PCO2 (PvCO2). This estimate of PvCO2 was combined with the end tidal PCO2 and CO2 production to give a non-invasive Fick estimate of the cardiac output. Non-invasive cardiac outputs correlated well with those measured by dye-dilution (r2 = 0.94) over a range of cardiac outputs from 490-7280 ml/min. All non-invasive determinations were within 15% of the line of identity, and within 22% of averaged replicate dye-dilution values. Our results agree with previous comparisons of indirect Fick-CO2 methods with invasive determinations of cardiac output. These data suggest that the indirect Fick-CO2 technique offers a rapid, non-invasive alternative to invasive monitoring of cardiac output.