The effect of moderate hypoglycemia (p-glucose, 2.0 +/- 0.3 mmol/L; mean +/- SD) on regional cerebral blood flow (rCBF) was studied in a group of 10 healthy, right-handed men (aged 23 to 28 years) using an intravenous xenon 133 single photon emission computed tomography technique (SPECT). After 10 minutes of hypoglycemia, global CBF had increased to 46.3 +/- 9.6 mL/100 g/min compared with the initial normoglycemic flow of 38.6 +/- 6.8 mL/100 g/min (P less than .01). The relative distribution of the rCBF changed significantly (P less than .05, ANOVA) from before to during hypoglycemia. Of the 10 regions analyzed, the highest increments in rCBF during hypoglycemia were found in the frontal (21.5% +/- 15.2%) and parietal (20.6% +/- 14.2%) lobes, and the lowest (10.7% +/- 9.4%) were found in the pons/brainstem regions. The increase in rCBF persisted for 15 minutes after normalization of blood glucose. The persisting high flow after hypoglycemia affected all regions, but a further 10.1% +/- 7.2% increase was observed in the pons/brainstem area (P less than .05). The CBF was significantly higher in the right compared with the left hemisphere (2.8%, 1.2%, and 3.9%, respectively; P less than .05) in all measurements. A decrease in brain volume was found at the final examination, compared with the hypoglycemic state (2.6%; P less than .05). It is concluded that moderate hypoglycemia leads to a marked increase in CBF and in the relative distribution of rCBF, which persists in the immediate period after normalization of the blood glucose level.