In order to evaluate the possible role of the hepatic macrophage (H-M macrophage) in lipopolysaccharide-induced shock and disseminated intravascular coagulation (DIC), a technique has been developed for the isolation and maintenance in culture of rabbit H-M macrophage. Characterization of the resultant cell population by morphology, nonspecific esterase staining, phagocytosis of latex beads, by presence of Fc and C3b membrane receptors confirms a pure population of M macrophage without outgrowth of other cell types for up to 10 days in culture. The exposure in vitro of the H-M macrophage to LPS (either Salmonella minnesota R595 or Escherichia coli 0111:B4) stimulates a selective increase in activity of several cellular enzyme: LDH, lysozyme, plasminogen activator, and a procoagulant factor, with minimal changes in acid phosphatase and beta-glucuronidase detected. Concomitantly, both in vivo and in vitro treatment with LPS produces an apparent direct cellular toxicity. The combined effect of toxicity and selective stimulation and release of mediators in LPS-stimulated H-M macrophage may play a central role in the endotoxemic shock syndrome.