Although recent studies have demonstrated a link between environmental contaminants exposure and obesity, the molecular mechanisms remain to be determined. Reduced expression of the hepatic lipolysis stimulated lipoprotein receptor (LSR), which is important for chylomicron clearance, is associated with increased body fat mass in mice. Since the polycylic aromatic hydrocarbon benzo[a]pyrene (B[a]P) is associated with weight gain in mice, the objective of this study was to determine if B[a]P modified hepatic LSR and lipid status. In 11-wk old male C57BL/6RJ mice treated with B[a]P (0.5 mg/kg, i.p. every 48h, 15 days), the increased weight gain was associated with increased plasma triglycerides and cholesterol, and increased liver cholesterol content as compared to control mice. LDL-receptor protein was decreased, and the positive correlation between hepatic LSR and LDL-receptor protein in control animals was absent in the B[a]P-treated mice, pointing towards a dysregulation of hepatic lipid homeostasis in the mice exposed to this pollutant. Hepa1-6 cells treated with 0.001 mM B[a]P also led to decreased LSR and LDL-receptor protein, as well as modified LSR activity as lipoprotein receptor. We propose that dysregulation of lipid homeostasis in the liver may contribute towards B[a]P-induced weight gain in mice.