The permeability-surface area product (PS) of [1-14C]docosahexaenoate and [1-14C]palmitate at the blood-retina (BRB) and blood-brain barrier (BBB) was determined after in situ brain perfusion in Sprague-Dawley rats. The intracarotid injection procedure involved continuous infusion of albumin-bound fatty acids for up to 20 s. In the retina, and visual, parietal and frontal cortex, there was a significant decrease in mean PSs for docosahexaenoate compared to the palmitate group. For optic nerve and tract, superior colliculus, lateral geniculate, striatum, hippocampus and olfactory bulb, the comparison of PS values between the two fatty acid-injected groups of animals did not reveal any difference. It is suggested that the lower docosahexaenoate transport, compared to 16:0, across microvascular endothelium of the retina and other cortical regions might help explain the highest availability and selective retention of the essential 22:6(n-3) fatty acid in these nervous system structures.