We have investigated the effects of polymyxin B and gentamicin on the histologic and biochemical alterations caused by D-galactosamine in the rat. Polymyxin B, but not gentamicin, protected against galactosamine-induced liver injury. There was good correlation between the biochemical data and the morphologic changes. This study suggests that endogenously produced endotoxin contributes to the extent of the hepatic damage caused by galactosamine. It is likely that the ability of the liver to detoxify small amounts of bacterial lipopolysaccharides absorbed from the gut is impaired after the preceding galactosamine injury.