SummaryTwo groups of normal volunteers had regional cerebral blood flow (rCBF) measured, by the133Xenon inhalation technique, before and 30 minutes after 250 mg or 500 mg caffeine given orally. rCBF was measured in a third group of subjects, twice, at a similar interval under identical laboratory conditions. Subjects who received caffeine showed significant decreases in rCBF while the others showed no rCBF change from the first to the second measurement. However, the two caffeine groups did not differ in degrees of rCBF reduction. There were no regional variations in the post-caffeine decrease in cerebral blood flow. The three groups did not show significant changes in end-tidal carbon dioxide, pulse rate, blood pressure, forehead skin temperature and respiratory rate.