Caco-2 cells and human colonic explants were compared for their ability to esterify lipid classes, synthesize apolipoproteins and assemble lipoproteins. Highly differentiated cells and colonic explants were incubated with [(14)C]oleic acid or [(35)S]methionine for 48 h. Caco-2 cells demonstrated a higher ability to incorporate [(14)C]oleic acid into cellular phospholipids (13-fold, P<0.005), triglycerides (28-fold, P<0.005) and cholesteryl ester (2-fold, P<0. 01). However, their medium/cell lipid ratio was 11 times lower, indicating a limited capacity to export newly synthesized lipids. De novo synthesis of apo B-48 and apo B-100 was markedly increased (7%0 and 240%, respectively), whereas the biogenesis of apo A-I was decreased (60%) in Caco-2 cells. The calculated apo B-48/apo B-100 ratio was substantially diminished (107%), suggesting less efficient mRNA editing in Caco-2 cells. When lipoprotein distribution was examined, it displayed a prevalence of VLDL and LDL, accompanied along with a lower proportion of chylomicron and HDL. In addition, differences in lipoprotein composition were evidenced between colonic explants and Caco-2 cells. Therefore, our findings stress the variance in the magnitude of lipid, apolipoprotein and lipoprotein synthesis and secretion between the two intestinal models. This may be due to various factors, including the origin of Caco-2 cell line, i.e., colon carcinoma.