The blood-brain barrier (B-BB) in 3-month-old rats was opened unilaterally by infusing 1.8 m L(+)arabinose in water into the internal carotid artery through a catheter in the external carotid. Two poorly penetrating uncharged test radiotracers of differing molecular weight and size, [14C]sucrose (340 daltons, radius 5 A) and [3H]inulin (5500 daltons, radius 15 A), were simultaneously injected i.v. in untreated rats, or rats at 1, 30, or 50 min after infusion of hypertonic arabinose solution. Evans-blue solution was injected 5 min prior to osmotic treatment as a visual indicator of barrier integrity. In regions of uninfused control brains, the [14C]sucrose permeability-surface area (PA) product approximated 10(-5) s-1, whereas PA was not measurable for [3H]inulin. In arabinose-infused animals, PA products on the ipsilateral hemisphere for both [14C]sucrose and [3H]inulin were markedly elevated 6 min after infusion, but decreased by 35 and 55 min. In nearly all regions, statistically significant differences were not found between 6-min [14C]sucrose- and [3H]inulin-PA values (P greater than 0.05). However, at 35 and 55 min in most regions, the PA for [3H]inulin was significantly lower (P less than 0.05) than PA for [14C]sucrose. The results indicated that the B-BB closed more rapidly to larger than to smaller molecules after osmotic treatment and were consistent with a pore model for osmotic B-BB opening.