Bacterial endotoxins have been shown to stimulate prostanoid production in vivo. This study compares the effect of endotoxin administered in vivo and in vitro on hepatic 14C arachidonic acid (AA) metabolism. Livers were perfused with either buffer, buffer containing endotoxin, or buffer containing endotoxin plus meclofenamate. Liver slices were then incubated with 14C AA, extracted, and chromatographed. In buffer perfused livers, 72 +/- 8 percent of the 14C label post incubation was associated with arachidonic acid. This was in contrast to nonperfused, fresh liver slices where 98 +/- 1 percent of the 14C label remained as arachidonic acid. Slices taken from perfused livers which received endotoxin in vitro had 72 +/- 9% of the label associated with AA. Meclofenamate treatment increased this percentage to 97 +/- 1%. Fresh liver slices incubated with endotoxin in vitro for 10 minutes demonstrated no significant increase in AA metabolism when compared to fresh slices. These data demonstrate that fresh liver slices metabolize very little exogenous AA. In contrast, the perfusion procedure alone is a significant stimulus for enhancing arachidonic acid metabolism. Subjecting liver tissue to endotoxin in vitro or in vivo for a one hour period is not a significant stimulus for enhanced AA metabolism.