We evaluated the effects of breathing 35% stable xenon in 65% oxygen on regional cerebral blood flow and the electroencephalogram in 20 normal volunteers. We measured blood flow in 32 brain regions over both hemispheres with the xenon-133 intravenous injection technique in two protocols. In the first protocol (n = 10), a baseline study was followed by a second study during 5 minutes of breathing stable xenon; in the other protocol (n = 8), the baseline study was followed by a second study after 5 minutes of breathing stable xenon. Two volunteers were excluded due to excessive movements during the inhalation of stable xenon. Some of the remaining 18 volunteers had varying alterations of consciousness accompanied by electroencephalogram changes. After stable xenon inhalation the electroencephalogram returned to normal within 2-3 minutes. During stable xenon inhalation mean +/- SD PECO2 dropped significantly from 39.4 +/- 4.4 to 33.3 +/- 5.4 mm Hg in the first protocol and from 39.4 +/- 2.6 to 34.8 +/- 4.1 mm Hg in the second protocol due to hyperventilation in 13 volunteers. Mean regional cerebral blood flow increased significantly by 13.5-25.4% without correction for PECO2. In the first protocol regional cerebral blood flow increased by greater than 12% in 11-14 (depending on the flow parameter) of the 20 hemispheres. In the second protocol regional cerebral blood flow increased by greater than 12% in 9-13 of the 16 hemispheres. We conclude that cautious interpretation is necessary in the assessment of regional cerebral blood flow with 35% xenon-enhanced computed tomography.