The amount of radioactivity in brain was estimated at different times after intracarotid injection in the pentobarbital-anesthetized rat. Fifteen seconds after injection, six radiolabeled solutes minimally metabolized by brain, 3H2O , isopropanol, nicotine, antipyrine, 3-O-methyglucose, and codeine, left the brain according to first-order kinetics. Two solutes metabolized by brain, lactic acid, and heroin, behaved in a more complex fashion. The behavior of the six nonmetabolized solutes was interpreted satisfactorily by a simple model in which the brain is treated as a single compartment. From the model, uptake at 15 s as a percentage of the dose is linearly related to the permeability when the uptake is low, i.e., 30% or less. In higher uptakes blood flow becomes increasingly important. The efflux rate is similarly related to permeability and blood flow, but additionally it depends inversely on brain space. The exchanges of 3H2O, isopropanol, and nicotine were determined almost solely by blood flow and brain space. Movements of codeine and 3-O-methylglucose depended primarily on permeability and those of antipyrine on both factors.