The decrease in protein synthesis and secretion caused by volatile anesthetics was investigated using Hartley male guinea pig liver slices. Precision-cut liver slices (250-300 mM thick) were incubated in sealed roller vials (3 slices/vial) containing Krebs-Hensleit buffer at 37 degrees C under 95% O2 atmosphere. Volatile anesthetics were injected through a teflon septa cap on a filter paper wick and vaporized to produce constant concentration in the medium. A concentration (1-2.1 mM) and time related (0-24) decrease in protein synthesis (3H-leucine incorporation) and secretion by halothane and d-halothane was observed. d-Halothane was less inhibiting than halothane. Inhibition was not on the uptake of the 3H-leucine but with its incorporation in the nascent peptide. The effects of enflurane (2.2 mM), isoflurane (2.2 mM), and sevoflurane (1.3 mM) on protein synthesis and secretion were also studied. The rank order of decrease in protein synthesis caused by the volatile anesthetics studied was halothane greater than isoflurane greater than enflurane greater than sevofluane greater than d-halothane. Enflurane, isoflurane, and sevoflurane increased the protein secretion while halothane and d-halothane caused a pronounced decrease. Alterations in protein synthesis and secretion appears to be an early and sensitive indicator of cytotoxin injury.