In order to investigate the effect of diazepam in reducing the incidence and severity of cholesterol induced atherosclerosis in rabbits, 3 treatment groups were compared. The control Group I received the laboratory diet alone. Group II received cholesterol (1 gm daily, given by syringe). Animals in Group III additionally received diazepam (3 mg/kg/day) orally, again by syringe. After 21 days, animals were injected with Evans blue and 3 hours later their aortas were removed and examined for permeability changes. Serum was assayed for various lipid and lipoprotein components. Cholesterol feeding produced a 10-fold increase in serum cholesterol values in Groups II and III compared to the control Group I. The aortic uptake of Evans blue was significantly increased in animals treated with cholesterol but not in those which simultaneously received diazepam. Thus, diazepam prevented the increased endothelial permeability produced by hypercholesterolaemia, but it is not yet clear whether this effect involves the central nervous system or is a consequence of some more local membrane stabilizing action.