Small unilamellar liposomes with an average diameter of 80 nm were prepared from phosphatidyl choline of various sources using the dialysis method with cholate as a detergent. When 14C-labeled soybean liposomes were intravenously injected into male NMRI mice, up to 10% of the total label was found in the liver lipid. The uptake was dose-dependent and reached an apparent saturation 4 h after injection. The liver maintained a constant radioactivity corresponding to 1.9 +/- 0.13 mg phospholipid/g liver until ten hours after injection of 850 mg labeled phosphatidyl choline/kg body wt. Little radioactivity was taken up by the spleen. Analogous doses of liposomes prepared from egg yolk phosphatidyl choline led to a radioactivity corresponding to 1.3 +/- 0.4 mg lipid/g liver 4 h after injection. Liposomes with a similar size were prepared from hydrated, i.e., saturated phosphatidyl choline. After intravenous administration of these liposomes, an amount of 5.3 +/- 0.5 mg labeled lipid was found per g liver after 4 h. In contrast to unsaturated liposomes, 5.8 +/- 0.8 mg lipid per gram spleen was trapped by the spleen. The pharmacodynamic effect of these different liposomes was studied in benzo[a]pyrene-pretreated mice intoxicated with 400 mg/kg paracetamol. Animals which received paracetamol exhibited serum alanine aminotransferase activities of 4220 +/- 1140 units/l after 4 h and exhaled 120 +/- 19 nmol ethane kg-1 h-1. When pretreated with 850 mg soybean phosphatidyl choline/kg body wt. (i.v.) 2 h prior to paracetamol, the increase in serum transaminase activity was reduced to 117 +/- 104 units/l and ethane exhalation amounted to 18 +/- 8 nmol kg-1 h-1. In contrast, similar pretreatment with egg yolk phosphatidyl choline or hydrated phosphatidyl choline failed to protect against paracetamol-induced hepatotoxicity. The different pharmacodynamic effects of the two phosphatidyl cholines of plant or animal origin cannot be explained on the basis of their different pharmacokinetics. In the case of soybean phosphatidyl choline liposomes, the amount of radioactive lipid found in the liver correlated with the hepatoprotective potency.