Rats were exposed to 1.3 gHz microwave energy to assess the uptake of several neutral polar substances in certain areas of the brain. A quantitative, radioactive isotope method, which uses an internal standard, was employed to measure the loss of test substances to brain tissue. Single, 20 min exposure, to either pulsed or continuous wave (CW) microwave energy induced an increase in the uptake of D-mannitol at average power densities of less than 3.0 mW/sp. cm. The permeability change was greatest in the medulla, followed, in decreasing order, by the cerebellum and hypothalamus, with small or negligible changes in the hippocampus and cortex. Permeability increases were observed for mannitol and inulin but not for dextran. Increased permeability was observed both immediately and 4 h after exposure, but not 24 h after exposure. After an initial rise, the permeability of cerebral vessels to saccharides decreased with increasing microwave power. Differences in the level of uptake occurred between CW energy and pulsed energy of the same average power. Microwaves of the same average power but different pulse characteristics also produced different uptake levels. Our findings suggest that microwaves induce a temporary change in the permeability for small molecular weight saccharides in the blood-brain barrier system of rats.