Treatment with high dose human growth hormone (GH), although an effective anabolic agent, has been associated with increased incidence of sepsis, inflammation, multiple organ failure and death in critically ill patients. We hypothesized that GH might increase mortality by exacerbating cholestasis, through modulation of bile acid transporter expression. High dose GH was continuously infused over four days into rats and on the final day LPS was injected. Hepatic bile acid transporter expression was measured by Northern analysis and immunoblotting, and compared with serum markers of cholestasis and endotoxinemia. Compared with non-GH treated controls, GH increased endotoxin-induced markers of cholestasis and liver damage, and augmented IL-6 induction. In endotoxinemia, GH treatment significantly induced Mrp1 mRNA and protein and suppressed Oatp1 and Oatp4 mRNA, suggesting impaired uptake of bilirubin and bile acids at the basolateral surface of the hepatocyte, which could contribute to the observed worsening of cholestasis by GH. This study of endotoxinemia may thus provide a mechanistic link between GH treatment and exacerbation of cholestasis through modulation of basolateral bile acid transporter expression in the rat hepatocyte.