The concept that relates intestinal bacteria and their toxins as a common pathway of liver injury by toxic agents has interested investigators for a long period. Recently, a number of studies in experimental animals and in patients with liver disease support this contention, and are reviewed. Evidence is presented to suggest that: (a) function of the sinusoidal cells is critical to integrity of the hepatocyte; (b) damage to these lining cells by several agents may be the initial injury leading to decreased ability of the liver to detoxify endotoxin (LPS); (c) following this primary injury to Kupffer and endothelial cells, LPS causes damage at amounts which are ordinarily innocuous and may represent a final pathway of liver necrosis; (d) "spillover" of LPS may lead to systemic manifestations of liver disease, and (e) modification of endotoxin toxicity or absorption may protect against several acute and chronic liver injuries.