The influence of bovine serum albumin (BSA) on the rat brain cortical swelling induced by sodium arachidonate and polyunsaturated fatty acids has been studied. Coincubation of arachidonate with BSA at a molar ratio of 5 (arachidonate/BSA) or less greater inhibited the arachidonate-induced swelling. As the molar ratio of arachidonate/BSA increased, the degree of swelling increased. The swelling was not reversed by BSA, although the BSA released 46% of the previously incorporated [3H]arachidonic acid from the cortical slices. The entry of [3H]arachidonate into the slice was completely abolished by 0.1 mM BSA or partially inhibited by exogenous arachidonate. It is concluded that the induction of brain swelling by arachidonate requires the intracellular transport of exogenous arachidonate.