An earlier study showed that unidirectional glucose transport from blood to brain decreases during perfusion with anoxic blood (Betz, A.L., Gilboe, D.D. and Drewes, L.R. (1974) Brain Res. 67, 307-316). Brain glucose levels also decrease during anoxia. Therefore, the present study was designed to investigate whether the decreased transport might be the result of decreased accelerative exchange diffusion when brain glucose levels are low. The rate of unidirectional transport into brain (v) of d-[6-3H]glucose was studied in 22 isolated, perfused dog brains by means of an indicator dilution technique using 22Na as the intravascular reference. The kinetics of transport were determined over a range of blood glucose concentrations (S1) at each of live different brain glucose levels (S2). The existence of accelerative exchange diffusion for glucose was indicated by a decrease in the intercept (increase of apparent V) of a double reciprocal plot ( 1 v versus 1 S1) as S2 increased. This phenomenon is consistent with a model for facilitated diffusion in which the mobility of the loaded carrier is greater than that of the unloaded carrier. Although the data predict a decrease in glucose transport during anoxia, the predicted decrease (5%) is less than the observed decrease (35%). It is concluded that the simple mobile-carrier model for facilitated diffusion cannot, by itself, describe all properties of blood-brain glucose transport.