As food in the intestine "drives" the enterohepatic circulation and bile acids influence bile flow, we postulated that the cholestasis of total parenteral nutrition might be due to bile acid changes, and the cholelithiasis and biliary sludge of total parenteral nutrition to bile lipid changes. We therefore studied bile acid and bile lipid metabolism in the following groups of rats, with and without bile fistula: (a) nonfasted, orally fed controls, (b) orally fed controls fasted for 20 h, and (c) after 7 days of total parenteral nutrition. Biliary bile acid concentration (35.4 +/- 2.5 mM) and secretion (253 +/- 20.0 mumol/100 g body wt.24 h) increased significantly in the rats on TPN and the rats fasted for 20 h (38.8 +/- 2.5 and 243 +/- 23.4 mM, respectively) when compared with the orally fed controls (26.5 +/- 2.5 and 178 +/- 23.5 mM, respectively). Bile flow, however, was unchanged. Bile acid pool size (Eriksson washout technique) also increased from 43.4 +/- 3.0 mumol/100 g body wt in the controls to 50.5 +/- 4.8 in the group fasted for 20 h and 65.6 +/- 5.3 in the TPN group (p less than 0.05-0.01). Similar bile acid pool sizes (carcass extraction method) were found in the nonfistulated animals. Biliary cholesterol secretion and saturation were significantly less in the TPN rats than in the other two groups. Liver microscopy indicated only minimal fatty change, but serum bile acid and alkaline phosphatase levels were increased in the TPN group (p less than 0.05). Thus, during TPN bile acids stagnate within the enterohepatic circulation, increasing biliary bile acid concentration and secretion rates and expanding the pool size. However, the absence of an associated choleresis, together with abnormal liver function tests, suggest that alterations in bile acid metabolism cause a relative cholestasis in this model.