The efficiency of cell-specific transfection by receptor-mediated uptake is improved by the use of cationic lipids. Asialogly-coprotein (AP) was conjugated to poly-L-lysine (PL) and complexed with the plasmid pCMVL that contains a luciferase reporter gene. The asialoglycoprotein-poly-L-lysine:pCMVL (AP-PL:pCMVL) complexes then were mixed with the cationic lipid dioctadecylamidoglycylspermine (DOGS). This complex was taken up by the hepatocyte-like cell line, Hep G2, via the asialo-glycoprotein receptor. The expression of luciferase in cells transfected with the DOGS/AP-PL: pCMVL complexes were significantly increased compared with AP-PL:pCMVL complexes without DOGS. The ratio of AP-PL to DOGS is an important determinant for both transfection efficiency and for maintaining receptor specificity. Therefore, cationic lipids significantly increased the efficiency of asialoglycoprotein receptor mediated transfection in the hepatoblastoma cell line, Hep G2. The use of cationic lipids with receptor-mediated gene delivery systems could potentially increase transfection efficiency yet maintain cell-target specificity.