Alteration of blood-brain barrier (BBB) permeability by 2450 MHz CW microwaves was assessed semi-quantitatively after intravenous injection of horseradish peroxidase (HRP) and exposure of conscious, unrestrained rats to incident power densities of 0, 20 or 65 mW/cm2 for 30, 90 or 180 min. Additional rats were exposed to ambient heat (42 +/- 2 degrees C) for 30 or 90 min. None of the brain regions studied, with the exception of the normally leaky pineal gland, showed extracellular HRP leakage attributable to microwave or thermally-induced breakdown of the blood-brain barrier. The mean ratio of HRP-labeled microvessel endothelium/total number of microvessels counted was determined for each brain region. Mean values for the cortex, hypothalamus, cerebellum and medulla of microwave-exposed and heated rats were consistently below those of corresponding sham levels. This decrease appeared to correlate inversely with power density and duration of exposure. Statistically significant deviation (P less than 0.05) from sham mean values occurred in the cortex, hypothalamus, cerebellum and medulla of animals made hyperthermic with ambient heat or exposure to microwaves at 65 mW/cm2 (specific absorption rate approximately equal to 13.0 W/kg) for 30 or 90 min. Additionally, electron microscopic evaluation of ultrathin sections taken from each of the 4 brain regions revealed no significant extravasation of HRP indicative of microwave or ambient heat-induced disruption of the blood-brain barrier.