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The liquid/gas partition coefficients of three inhalation anesthetics in Fluosol-DA 20% (Fluosol), a perfluorocarbon blood substitute, were determined in vitro. The high values found (6.68 for halothane, 7.54 for enflurane, and 7.20 for isoflurane) suggested that induction with these agents would be prolonged in patients treated with Fluosol. Induction of isoflurane anesthesia (as a representative agent) at constant inspired concentration was studied in five mongrel dogs before and after replacement of about 25% of each animal's blood volume with Fluosol. Inspired and end-tidal isoflurane and carbon dioxide concentrations were recorded breath by breath, together with cardiac output. There was a significant delay in rise of end-tidal isoflurane concentration after Fluosol infusion. However, because cardiac output could not be held constant during each experiment, and because cardiac output also affects the rate of rise of alveolar anesthetic concentration, a physiological computer model was used to compare the isoflurane blood/gas partition coefficients that must have existed to account for the observed end-tidal levels before and after Fluosol infusion, while taking cardiac output variation into account. Post-Fluosol blood/gas partition coefficients calculated in this way (2.59 +/- 0.51 SD) were significantly different (P less than 0.001) from pre-Fluosol levels (1.45 +/- 0.15 SD) and were not significantly different from post-Fluosol partition coefficients calculated by volume-weighted averaging (2.91 +/- 0.36 SD). This indicates that the delay observed was attributable in large part to increased solubility of isoflurane in blood after addition of Fluosol. Based on their similar liquid/gas partition coefficients in Fluosol, similar delays should occur with halothane and enflurane.