Dietary vegetable proteins may lower plasma cholesterol compared to animal proteins. We considered the possibility that lower digestibility and the trypsin inhibitor (TI) content of plant proteins could lead to alterations in bile acid metabolism and exocrine pancreatic function mediating some of this change. Mice were fed cholesterolemic diets of different protein source and TI content: casein, soy protein isolate, or casein plus TI for 4 weeks. Plasma and liver cholesterol were measured; pancreata, intestinal contents and mucosal scrapes were collected for bile acid, trypsin, chymotrypsin, amylase, and lipase assays. The soy group had lower plasma cholesterol levels. Intestinal bile acids in this group were higher, suggesting a causal relationship (increased bile acid secretion leading to increased cholesterol catabolism). Conversely, liver cholesterol in this group was raised, reflecting a possible shift in body cholesterol pools. TI addition did not affect lipid metabolism, though it did affect pancreatic function: it led to increased pancreatic weight and depressed intestinal trypsin activity, but elevated chymotrypsin and amylase levels in pancreas and intestine and increased trypsin levels in the pancreas. Therefore, soybean TI does not seem to affect cholesterol metabolism, though it greatly affects pancreatic secretion. On the other hand, soy protein has a marked effect on the bile acid and cholesterol metabolism, which may be a function of protein quality.