The effect of basal insulin on global and regional brain glucose uptake and metabolism in humans was studied using 18-fluorodeoxyglucose and positron emission tomography (FDG-PET). Eight healthy male volunteers aged 49.3 +/- 5.1 years were studied twice in random order. On each occasion, they received an infusion of 0.1 mg. kg(-1). min(-1) somatostatin to suppress endogenous insulin production. In one study 0.3 mU. kg(-1). min(-1) insulin was infused to replace basal circulating insulin levels, and in the other study a saline infusion was used as control. We sought stimulatory effects of basal insulin on brain glucose metabolism particularly in regions with deficiencies in the blood-brain barrier and high density of insulin receptors. Insulin levels were 27.07 +/- 1.3 mU/l with insulin replacement and 3.51 +/- 0.4 mU/l without (P = 0.001). Mean global rate of brain glucose utilization was 0.215 +/- 0.030 mmol. kg(-1). min(-1) without insulin and 0.245 +/- 0.021 mmol. kg(-1). min(-1) with insulin (P = 0.008, an average difference of 15.3 +/- 12.5%). Regional analysis using statistical parametric mapping showed that the effect of basal insulin was significantly less in the cerebellum (Z = 5.53, corrected P = 0.031). We conclude that basal insulin has a role in regulating global brain glucose uptake in humans, mostly marked in cortical areas.