Hyperlipidemia aggravates progressive glomerulo-sclerosis in renal failure. The role of abnormalities of intermediate (IDL) and low density lipoproteins(LDL) in the development of focal and segmental glomerulosclerosis (FSGS) in the nephrotic syndrome has not been elucidated. Abnormal glomerular cell uptake of cholesterol may be a trigger for FSGS. We have examined the uptake into U937 cells of IDL and LDL obtained from nephrotic sera. U937 is a monocytic cell line derived from histiocytic lymphoma that lacks the capacity for endogenous cholesterol synthesis. Growth of these cells in vitro therefore is dependent on the uptake of lipoproteins which supply exogenous cholesterol, the rate of which can be used as a convenient measure of cholesterol uptake. Sera from five nephrotic children were collected on initial presentation and before treatment with steroids. Five age- and sex-matched healthy children with normal lipid profiles were used as controls. The IDL and LDL in the sera were separated by fractional ultracentrifugation. The IDL at 0, 5 and 10μmol/L cholesterol concentrations and LDL at 0, 50, and 100 μmol/L cholesterol concentrations were added to 1.5 × 105/ml inoculate of U937 cells. The growth of U937 cells was measured by electronic cell counter at 48, 72, 96 and 120 hours. The cholesterol/triglyceride ratio of IDL particles from nephrotic sera was elevated as compared to normal (1.803± 0.27 vs 1.036 ± 0.14, mean ± SEM, p<0.05) and the particle size larger (p<0.001). The growth of U937 cells was significantly greater in the presence of IDL and LDL cholesterol from nephrotic children, compared to growth in the presence of control cholesterol (p<0.001). This effect was seen at 48, 72, 96 and 120 hours of incubation. The experiment was repeated using pre-incubation with monoclonal antibody against LDL-receptor. The monoclonal antibody was able to block the growth promoting effect of normal cholesterol on U937 cells. Nephrotic cholesterol promoted growth of U937 cells; inspite of pre-incubation with monoclonal LDL receptor blocking antibody. These data suggest that IDL and LDL from nephrotic children are taken up by U937 cells more avidly than those from normal children. The mechanism may relate to cholesterol enrichment and altered receptor-mediated binding of these particles.