Methylphenidate (MPH) is the first choice of medical treatment for attention-deficit/hyperactivity disorder (ADHD). Its mechanism of action is to inhibit the reuptake of dopamine and noradrenaline mainly in the region of the striatum. It has been estimated that 10-30 % of patients with ADHD do not respond adequately to MPH. The aim of this study was to evaluate whether striatal differences exist between good and poor responders to MPH. The sample included 27 treatment-naïve children with ADHD between the ages of 6 and 14. MPH administration started 1 day after the MRI acquisition. After a month, psychiatrists established the good or poor response to treatment according to clinical criteria. MRI images were analyzed using a technique based on regions of interest applied specifically to the caudate and accumbens nuclei. Sixteen patients showed good response to MPH and 11 a poor one. Regions of interest analysis showed that good responders had a higher concentration of gray matter in the head of both caudate nuclei and the right nucleus accumbens. Furthermore, a significant correlation was found between caudate and accumbens nuclei volume and the Conners' Parent Rating Scale and Continuous Performance Test improvement. These results support the hypothesis of the involvement of the caudate and accumbens nuclei in MPH response and in ADHD pathophysiology.