Hyperlipidemia in the nephrotic syndrome results from increased synthesis and decreased catabolism of lipoproteins. The contribution of each to establishing blood lipid levels is unknown. Increased triglyceride rich lipoprotein concentration, very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) primarily results from decreased clearance. This defect is due in part to reduced lipoprotein lipase (LPL) on the vascular endothelium resulting either from decreased synthesis or inadequate binding of this enzyme to endothelial surfaces. In contrast, both low density lipoprotein (LDL) and lipoprotein(a) [Lp(a)] concentrations are increased. Unlike the case of albumin or transferrin, or apoA-I in the rat, LDL apoB 100 synthesis is not related to that of albumin, suggesting a different mechanism of regulation or a response to a stimulus that is not the same as that augmenting the synthesis of nonlipoproteins. Evidence is presented for synthesis of LDL through a mechanism that bypasses the normal delipidation pathway that requires a VLDL precursor for LDL formation. HDL concentration is normal but maturation is impaired leading to a shift from the larger HDL2 to the smaller HDL3, a variant that is less effective as a transporter of the LPL cofactor apolipoprotein C II.