In man, atherosclerosis and its associated complications are the leading causes of death in many countries today. Numerous studies have shown a positive correlation between the blood levels of cholesterol (1, 2) and possibly triglycerides ( 3 ) , and the incidence of this disease. Therefore, an agent capable of reducing blood levels of cholesterol and triglycerides may be of clinical value in various hypercholesteremic and hyperlipidemic states. In our experimental investigations for hypolipemic drugs, 2 -acetoamidoethyl (p-chlorophenyl) (m-trifluoromethylphenoxy ) acetate (halofenate) (4) affects a number of important plasma lipid parameters in the rat.Methods and MateriaZs. Holtzman male albino rats weighing 130-140 g were maintained on Purina Laboratory Chow for approximately 1 week. Thereafter, the rats were randomized by weight into groups of 10 rats (each averaging 165 g body weight) and placed on the experimental diets. The rats were housed on wire, 10 to a cage, and were given food and water ad libitum.The control diet consisted of (%): Labco casein, 20, sucrose, 72, cellulose, 2, salt mixture (S), 4, corn oil, 1, and dl-methionine, 0.5. A vitamin mixture was added that supplied (mg for each 100 g of diet): vitamin A palmitate, 0.4; calciferol, 0.005 ; menadione, 1 ; a-tocopheral acetate, 4; thiamine-HC1, 0.8; riboflavin, 1.6; pyridoxineHC1, 0.8; niacinamide, 4.0; calcium pantothenate, 4.4; para-aminobenzoic acid, 4.0; inositol, 20; biotin, 0.02; folic acid, 0.2; choline bitartrate, 400; and vitamin B12, 0.03; as a 0.1% trituration in mannitol. Test compounds were added at the expense of equal weights of sucrose.The test diets were fed for 9 days. At the conclusion of the test period, using light nem-butal anesthesia, 5 ml of cardiac !blood were taken and placed in tubes containing 0.5 ml of 0.4 M sodium citrate. Plasma was obtained by centrifugation for the determination of total cholesterol by the method of Abell et al. (6), triglycerides by the method of Van Handel and Zilversmit ( 7 ) as modified by Carlson (8) , phospholipids by the method of Morrison ( 9 ) ) and free fatty acids by the method of Dole and Meinertz (10). Nine-day total body weights and liver weights were also determined.Results and Discussion. Using 10 rats in each group, Table I shows the effect of halofenate at multiple dose levels on four plasma lipid parameters [Cholesterol (chol) , triglyceride (TG) , phospholipids (PL) , and free fatty acids (FFA) 1.Effect on plasma lipids. Halofenate, when administered orally to rats by incorporation into the diet for 9 days, significantly reduced the plasma cholesterol level. The drug was incorporated in the diet a t levels ranging from 0.00625 to 0.05% and showed a dose-response effect. A small (12%), but significant reduction was obtained at the 0.00625% level with an average lowering of. 40% at the 0.05% drug level.Halofenate also reduced the plasma triglyceride level. In general, this reduction parallels the plasma cholesterol depression. Plasma triglyceride concentrations are subject to ...