Certain oxygenated derivatives of cholesterol have dramatic effects on cholesterol synthesis. The present study compared the effects of cholesterol and an oxygenated metabolite, cholesterol-alpha-epoxide, on sterol metabolism in rats. Sterol balance measurements using isotopic and chromatographic techniques were carried out in rats fed liquid control diets, control diets + cholesterol (1 mg/ml), and control diets + cholesterol-alpha-epoxide (1 mg/ml). Sterol metabolism was affected by both cholesterol and cholesterol-alpha-epoxide. Cholesterol feeding decreased cholesterol synthesis (-9.57 +/- 7.23 mg/day), increased endogenous bile acid synthesis (7.71 +/- 1.18 mg/day), and increased cholesterol turnover (7.78 +/- 2.33 mg/day) compared to controls. Cholesterol-alpha-epoxide had no effect on cholesterol synthesis, endogenous bile acid synthesis and cholesterol turnover compared to controls. However, animals fed cholesterol-alpha-epoxide had large increases in total acidic steroid output (determined by chromatographic analysis, 12.33 +/- 4.05 mg/day). This finding suggests that cholesterol-alpha-epoxide is absorbed and converted to bile acids. Apparently, the epoxide enters the bile acid biosynthetic pathway distal to the rate-limiting step of 7 alpha-hydroxylation. As a result, large amounts of bile acids are formed from the epoxide without affecting endogenous cholesterol or bile acid synthesis. This was confirmed in a separate experiment by feeding [4-14C]cholesterol-alpha-epoxide and recovering labeled bile acids (hyodeoxycholic acid and lithyocholic acid) as well as the starting radioactively labeled epoxide in the feces.