Alterations in lipoprotein levels are reported to be related to an increased risk of gallstones. Plasma lipid metabolism is regulated by a number of proteins that are polymorphic in the population. The present research was designed to investigate the association between the polymorphisms of these proteins and the presence of various gallbladder diseases. Restriction fragment length polymorphisms (RFLPs) of apolipoprotein B (XbaI, EcoRI), apolipoprotein A-I (PstI, MspI), and cholesteryl ester transfer protein (CETP) (EcoNI, TaqIA, TaqIB) genes were examined in a series of 210 cholecystectomy patients operated on for symptomatic gallbladder disease and in 92 healthy controls. The patients were categorized into four groups according to the type of gallstones and the presence or absence of cholesterolosis. The distribution of CETP TaqIB polymorphism in the patients with cholesterol gallstones differed significantly from that in the controls, with the B1B1 jects (39.7%) (P = 0.036). The patients with both cholesterol and non-cholesterol stones had lower high density lipoprotein (HDL)-cholesterol levels than the control subjects. However, the most distinct difference was found in the gallstone patients with the B2B2 genotype (P = 0.006). The frequency of the X1X1 genotype of the apolipoprotein B XbaI polymorphism was markedly higher in the patients with acalculous cholesterolosis (48.9%) or cholesterolosis with stones (58.1%) than in the gallstone patients with cholesterol stones (27.2%) or with non-cholesterol stones (34.1%) (P = 0.002). The present data suggest that CETP gene polymorphism may ba associated with cholesterol gallstone disease, probably in combination with some additional factor that reduces the plasma HDL cholesterol concentration, especially in TaqIB B2B2 genotype.(ABSTRACT TRUNCATED AT 250 WORDS)