Gemfibrozil, like clofibrate, is effective in lowering both serum cholesterol and triglycerides and in increasing high-density lipoproteins. The information available about its effects on biliary lipids is still limited, and conflicting results have been reported. In this study we evaluated the effect of gemfibrozil (1.2 g/day) and clofibrate (2.0 g/day), in a single-blind crossover design for 6 weeks with a 4-week washout period, on the biliary cholesterol saturation index (SI) in stimulated hepatic bile and on the hepatic secretion rate of biliary lipids in patients with hyperlipidemia. Clofibrate increased cholesterol SI (from 1.70 +/- 0.14 to 2.05 +/- 0.24), whereas gemfibrozil decreased it (from 1.70 +/- 0.14 to 1.54 +/- 0.16). The results were not statistically significant. The hepatic secretion rate of cholesterol was significantly (p less than 0.04) increased by clofibrate therapy, whereas it was significantly (p less than 0.04) decreased after gemfibrozil; a significant (p less than 0.04) decrease in the hepatic secretion rate of bile acids, bile acid pool size, and bile acid fecal excretion (p less than 0.04) was also found after gemfibrozil administration. Gemfibrozil interferes extensively with bile acid metabolism, but it does not increase biliary cholesterol secretion, as clofibrate does. These results suggest that gemfibrozil does not seem to increase the risk of gallstone formation in patients with hyperlipidemia.