Previous studies have shown that intraperitoneal bile increases bacterial growth and mortality in Escherichia coli peritonitis in the rat. The purpose of the present study was to determine a) the influence of bile acids (cholic, deoxycholic, or chenodeoxycholic) and bilirubin on survival, bacterial growth, and superoxide release by peritoneal phagocytes in this model, and b) the effect of bile acids on bacterial growth and endotoxin release when incubated with E. coli in vitro. Each of the bile acids aggravated the E. coli peritonitis, with increased bacterial counts in the peritoneal cavity and in blood and increased mortality. Deoxycholic acid was the most deleterious of the bile acids, causing suppression of superoxide release by peritoneal phagocytes, like whole bile. In vitro, bile acids did not seem to affect growth of E. coli, but cholic and deoxycholic acid seemed to enhance the release of endotoxin. It is concluded that the bile acids are responsible for the noxious effect of bile in E. coli peritonitis. It is suggested that the detergent properties of bile acids aggravate the peritonitis by solubilizing the cell membranes of both bacteria and phagocytes.