Rats were treated with heat-killed Propionibacteriurn acne8 and subsequent injection of a small amount of lipopolysaccharide after 7 days. After 24 hr most of the rats died of massive liver cell necrosis. Nonparenchymal liver cells were isolated from this liver injury model and incubated with arachidonic acid. Reverse-phase high-pressure liquid chromatography detected the 6-lipoxygenase metabolites (leukotriene B, and 6-hydroxy-arachidonic acid), whereas these compounds were produced in negligible amounts when the rats were treated with P. acnes only. Immunohistochemical studies with 5-lipoxygenase antiserum revealed that the injured livers contained a large number of positively stained round cells with segmented nuclei, which were rarely found in the livers treated with P. acnes only. These positively stained cells were histologically identified as neutrophils. The results suggested that the increased 6-lipoxygenase activity in the injured rat liver is attributable to the infiltrating neutrophils rather than to nonparenchymal hepatic cells. (HEPATOLOGY 1992; 16:462-468.) Leukotrienes (LTs) are lipid mediators of inflammation and anaphylaxis (1) formed during the host inflammatory response in such cells as neutrophils, eosinophils, monocytes, macrophages and mast cells (2). LT biosynthesis is initiated by arachidonate 5-lipoxygenase, an enzyme that converts arachidonic acid to LTA, (3). LTA, is further metabolized to LTB, or peptide LTs (LTC,, LTD, and LTE,) (1). These LTs represent relatively new compounds among a variety of mediators of inflammation. They are presumed to be involved in various liver injury models induced in rats or mice by CC1, (4-61, D-galactosamine plus lipopolysac-~~ ~