The effects of partial blood exchange with Fluosol-DA on hepatic microsomal oxidative metabolism have been studied in the rat. Antipyrine clearance (Cl) was used as an in-vivo measure of the activity of the mixed function oxidase system. Rats were partially exchanged with Fluosol-DA and dosed with antipyrine at selected time intervals following exchange. No change in antipyrine Cl was observed at 0.5 h, but there was a statistically significant decrease at 24 h and then an increase by more than 50% relative to control at 48 and 72 h. These data indicate that the effects of Fluosol-DA on hepatic function are time-dependent and that Fluosol-DA has the potential both to inhibit and to enhance hepatic metabolism. The possibility of altered hepatic metabolism should be considered when patients transfused with Fluosol-DA are given drugs primarily metabolized by the mixed function oxidase system.