A new generation of perfluorocarbon emulsions is being clinically evaluated as erythrocyte substitutes. However, the effect of perfluorocarbon emulsions on optical densitometric measurements of percent oxyhemoglobin (%O2Hb) has not been fully characterized. The purpose of this study is to quantify the effect of blood perfluorochemical concentration and hematocrit (Hct) on %O2Hb measurements. The authors hypothesize that perfluorocarbon emulsions affect the accuracy of %O2Hb measurements, and that the effect of perfluorochemical concentration and Hct on these measurements can be mathematically described. Porcine blood was used in this experiment. Blood with a Hct of 18% or 9% was mixed with a perfluorocarbon emulsion (Oxygent [AF0142]; Alliance Pharmaceutical Corporation, San Diego, CA). The concentrations tested were 0 g (Group 1; n = 69 measurements for a Hct of 18%, and n = 35 measurements for a Hct of 9%), 0.73 g (Group II; n =47 at 18%, n = 33 at 9%), 1.45 g (Group III; n = 46 at 18%, n = 30 at 9%), and 2.90 g (Group IV; n = 45 at 18%, n = 31 at 9%) of perfluorochemical per deciliter of blood (g PFC/dl). A tonometer was used to establish a range of oxygen tensions within each group while maintaining physiologic pH and PCO2. Error in %O2Hb measurements increases with higher perfluorochemical concentrations and lower Hct values. These errors in %O2Hb measurements are predictable; as such, an equation for correcting %O2Hb measurements in perfluorocarbon supplemented blood can be generated.