The factors controlling the transfection efficiency of cationic transfection efficiency was dependent on both DOTMA to lipid carrier systems following intravenous administration DNA, and DOTMA to Tween 80 ratios. Among the organs are poorly understood. Using N-[1-(2,3-dioleoyloxy)propyl]-examined, the lung appeared to be more transfectable than N,N,N-trimethylammonium chloride (DOTMA) combined other organs. A better transfection activity was obtained with Tween 80 as a carrier system and cDNA of luciferase with higher DOTMA to DNA and DOTMA to Tween 80 or -galactosidase gene as a reporter, we investigated the ratios. Time-response curve shows that gene expression importance of DOTMA to DNA ratio and the ratio of was transient with a maximal level between 10 and 24 h DOTMA to Tween 80 in the lipid formulation in determining after injection. Results from tissue distribution studies with the site and level of transgene expression following intra-125 I-labeled plasmid DNA and Southern analysis suggest venous administration. The data show that all of the that the transient expression is the result of the loss of internal organs, including lung, liver, spleen, heart and kidtransgene from the transfected cells. These results suggest neys, expressed the transgene upon systemic administhat cationic lipid-based delivery systems can be efficient tration into animals with 25 g of plasmid DNA when comfor gene delivery if the composition of the DNA-lipid complexed with DOTMA-Tween 80 lipid formulation. The plexes is properly controlled.