Prostaglandin E2(PGE2) is a very important immunosuppressive substance that is synthesized and released by all macrophages including KupfFer cells (KCs). In this study the changes of PGE2released by KCs were evaluated in a burned guinea pig model. Prostaglandin E2was releaesd by KCs from burned guinea pigs at a consistently and significantly high level when stimulated with endotoxin. On postburn day 82KCs that were cocultured with hepatocytes released significantly less PGE2. There was also a significant decrease in antibody-dependent cell-mediated cytotoxicity on postburn day 1. Kupffer cells can mediate immune suppression in burn injury by a prolonged increased production of PGE2that has immunosuppressive effects on other cells and by a decreased cytotoxic effect soon after burn injury.