In cholesterol-fed rats 6 weeks after partial ileal bypass, there was a significant (56%) decrease in serum cholesterol. Also, the concentration of very low density lipoprotein (VLDL) cholesterol was dramatically reduced after operation. However, after the operation, the percentage of high density lipoprotein (HDL) cholesterol was very high, i.e., 45% of the total lipoprotein cholesterol, whereas it was only 25% before operation. The initial rate of lecithin:cholesterol acyltransferase (LCAT), when assayed according to Stokke & Norum, showed an increase from 29 +/- 2 mumole/ml/h for non-operated cholesterol-fed controls to 121 +/- 7 mumole/ml/h after operation (p less than 0.01). After intestinal bypass the extrahepatic triglyceride lipase activity in serum was reduced by 60%, and there was no significant difference in hepatic triglyceride lipase. These observations indicate that in partial ileal bypass, the low serum cholesterol is due to the high HDL cholesterol and the high LCAT activity.