Functional magnetic resonance imaging (fMRI) was used to measure the effects of acute hypoglycemia caused by passive sensory Stimulation oil brain activation. Visual stimulation was used to generate blood-oxygen-level-dependent (BOLD) contrast. which was monitored during hyperinsulinemic hypoglycemic and euglycemic clamp studies. Hypoglycemia (50 divided by 1 mg glucose/dl) decreased the fMRI signal relative to euglycemia in 10 healthy human subjects; the fractional signal change was reduced by 28 divided by 12% (P < .05). These changes were were reversed when euglycemia was restored. These data provide a basis of comparison for studies that quantify hypoglycemia-related changes in fMRI activity during cognitive tasks based on visual stimuli and demonstrate that variations in blood glucose levels may modulate BOLD signals in the healthy brain. (C) 2006 Elsevier Inc. All rights reserved.