We tried to prove the hypothesis that apolipoproteins, the protein constituents of plasma lipoproteins, are secreted into bile. We examined human gallbladder bile obtained at surgery (N=54) from subjects with (N=44) and without (N=10) gallstones and hepatic bile collected by T-tube drainage (N=9) after cholecystectomy.<br>Using specific radioimmunoassays for human apolipoproteins A-I and A-II, the major apolipo-proteins of high density lipoproteins, for apolipo-proteins C-II and C-III, major apolipoproteins of very low density lipoproteins, we found immuno-reactivity for these four apolipoproteins in every bile samples.<br>Using immunodiffusion technique, we observed complete lines of identity between bile samples and purified apolipoproteins A-I and A-II, or C-II.<br>Using molecular sieve chromatography, we found identical elution profiles of biliary apolipo-proteins A-I and A-II, as those of apolipoproteins A-I and A-II purified from human plasma.<br>When we added high density lipoproteins purified from human plasma to lipoprotein-free solutions perfusing through isolated rat livers, we detected apolipoproteins A-I and A-II in bile.<br>These data indicate that apolipoproteins can be transported across the hepatocyte and secreted into bile.