The ability of mixed venous oxygen saturation (SvO2) monitoring to reflect changes in cardiac index (CI) with therapy in critically ill patients is unclear. To this end, SvO2 and CI were measured before and during an infusion of enoximone and/or dobutamine in 30 patients with advanced heart failure. A nonlinear relationship was observed between SvO2 and CI with the nonlinear correlation coefficient being 0.52. On normalizing for individual differences in hemoglobin and oxygen consumption, this correlation coefficient became 0.90. Further analysis of individual data was performed using linear regression, and the slopes and correlation coefficients were found to span a wide range slope: -10.0 to 30.9 min-m2/L, r: -0.27 to 0.99). However, the mean slope and correlation coefficient for patients with baseline CI and SvO2 less than 21/min/m2 and less than 55 percent were 18.3 min-m2/L and 0.87, respectively, while those for the remainder of patients were only 3.1 min-m2/L and 0.42, respectively. Thus, the nonlinear correlation coefficient of the SvO2-CI relationship in a group of patients is dependent on the homogeneity of their oxygen consumption and hemoglobin concentration. Furthermore, the ability of SvO2 to serve as a therapeutic indicator in any given patient is dependent on baseline SvO2 and CI.