General anesthesia has been shown to have a significant impact on the inflammatory response. We hypothesized that lung pathophysiology will be attenuated in a mouse model of secondary multiple organ dysfunction syndrome (MODS) elicited by intraperitoneal zymosan suspension in saline. CD-1 mice were anesthetized for 6 h with either 1% halothane or 1.5% isoflurane in 30% oxygen in N2 carrier gas. Another group of mice was exposed to 30% oxygen in N2 carrier gas only. The inflammatory response to zymosan was quantified by measuring lung myeloperoxidase activity (neutrophil recruitment). Lung injury was estimated by determining the degree of lung permeability to radioactive albumin (permeability index). Unanesthetized injured mice exhibited maximal lung myeloperoxidase activity 2 h after zymosan injection (.671 +/- .07 delta OD.min-1), which was significantly attenuated (p < .01) in injured mice anesthetized with halothane (.369 +/- .054) and isoflurane (.324 +/- .055). The maximum lung permeability index occurred 8 h after injection in the unanesthetized, injured mice (.398 +/- .019), and was attenuated (p < .01) in injured mice anesthetized with halothane (.255 +/- .02) and isoflurane (.224 +/- .019). Histopathological findings corresponded to the quantitative myeloperoxidase and permeability index values. Halothane and isoflurane attenuate lung inflammation and injury in this mouse model of multiple organ dysfunction syndrome. This attenuation may be related to modulation of the inflammatory response by volatile anesthetics.