Ventriculocisternal perfusions of mongrel dogs were performed for 1-6 h with solutions containing isotopically labeled compounds. At the conclusion of the perfusion period, serial brain samples were taken from the caudate nucleus and analyzed for radioactivity. Tissue concentration profiles were constructed from the data, and apparent tissue diffusion and capillary exchange coefficients were determined. The tissue diffusion constant of sucrose was 3 X 10(-6) cm2/s, which is approximately 45% of its free-water value. The permeability of the brain capillary complex to creatinine, sodium, and mannitol was so low that it could not be accurately measured by this technique. Capillary transfer coefficients, expressed as half-times, were determined for water, urea, and ethylene glycol; the t1/2 values were 1.5, 15, and 17 min, respectively. These numbers were converted to PS products and compared to other published values. This work suggests that the exchange of these compounds between blood and brain is partially (water) or nearly completely (urea and ethylene glycol) limited to membrane permeability.