Eating simple sugars has been suggested as having adverse behavioral and cognitive effects in children with attention deficit disorder (ADD), but a physiologic mechanism has not been established. To address this issue, metabolic, hormonal, and cognitive responses to a standard oral glucose load (1.75 g/kg) were compared in 17 children with ADD and 11 control children. Baseline and oral glucose-stimulated plasma glucose and insulin levels were similar in both groups, including the nadir glucose level 3-5 h after oral glucose (3.5 +/- 0.2 mmol/L in ADD and 3.3 +/- 0.2 mmol/L in control children). The late glucose fall stimulated a rise in plasma epinephrine that was nearly 50% lower in ADD than in control children (1212 +/- 202 pmol/L versus 2228 +/- 436 pmol/L, p < 0.02). Plasma norepinephrine levels were also lower in ADD than in control children, whereas growth hormone and glucagon concentrations did not differ between the groups. Matching test scores were lower and reaction times faster in ADD than in control children before and after oral glucose, and both groups showed a deterioration on the continuous performance test in association with the late fall in glucose and rise in epinephrine. These data suggest that children with ADD have a general impairment of sympathetic activation involving adrenomedullary as well as well as central catecholamine regulation.