The blood-retina and blood-brain transport of fatty acids was studied in control and lipid hydroperoxide-treated rats by measuring the permeability-surface area product (PS) to [1-14C]palmitate. An in situ carotid perfusion method was used. PS values were evaluated: (1) just after intracarotid injection of hydroperoxides; or (2) after a short-term systemic treatment for 1 week with sonicated emulsion of phospholipids-linoleate peroxidized mixture. Compared with saline-treated rats, PS remarkably decreased in the retina and most brain regions studied after acute, arterial injection of hydroperoxide preparations. On the contrary, the transport index significantly increased in the retina and almost all the brain areas after 7 days i.v. treatment with hydroperoxide emulsion. It is suggested that hydroperoxides acutely administered before transport radiotracer brought about a reinforcement of microvasculature junctional area or hampered substrate diffusion across endothelial membrane. On the other hand, upon short-term i.v. administration, hydroperoxides presumably triggered a lipid structure derangement of endothelial cell membranes and zonulae occludens due to their local accumulation and/or high capability of generating oxygen-free radicals.