OBJECTIVE To study the function of the hypothalamus-pituitary-adrenal (HPA) axis in children with attention deficit hyperactivity disorder (ADHD). METHODS One hundred and twenty-eight boys with ADHD at ages of 6 to 14 years were enrolled. The diagnosis and grouping of ADHD were based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV): ADHD-predominantly inattention type (ADHD-I, n=44), ADHD-predominantly hyperactive impulsivetype (ADHD-HI, n=32) and ADHD-combined type (ADHD-C, n=52). Thirty healthy boys served as the control group. Plasma levels of cortisol and adrenocorticotropic hormone (ACTH) were measured by automatic particle enzyme immunoassay and electrochemiluminescence respectively at 8:00 am. The intelligence level was tested by Raven's standard progressive matrices. RESULTS The children with ADHD had lower IQ score (84.5 + or - 11.3) than the control group (94.6 + or - 12.4) (p<0.01). There were significant differences in the IQ score among the three ADHD subgroups (p<0.01). The IQ score in the ADHD-I and the ADHD-C groups was significantly lower than that in the control group. The mean plasma cortisol level in the ADHD group (226.5 + or - 129.1 nmol/L) was significantly lower than that in the control group (384.5 + or - 141.4 nmol/L) (p<0.01). The three ADHD subgroups showed significantly decreased plasma cortisol level compared with the control group (p<0.01). The plasma level of cortisol was the lowest in the ADHD-HI group (154.4 + or - 71.6 nmol/L), followed by the ADHD I group (219.4 + or - 117.7 nmol/L) and the ADHD-C group (258.3 + or - 136.4 nmol/L). There were no significant differences in plasma concentration of ACTH between ADHD and control children. CONCLUSIONS In the non-stress state, the HPA axis may be dysfunctional in children with ADHD, which may be attributed to the under reactivity of the HPA axis. Lower plasma cortisol has fewer impacts on the cognitive-behavior function, but it may closely be related to attention deficit, hyperactivity and impulsive behaviors.