Clinical, animal and neuroanatomical studies of differential isomer and dosage effects of CNS stimulant medications on behaviour are reviewed. Wender's hypothesis that an underlying biochemical abnormality and a disorder of reinforcement was the primary deficit in “MBD” children is restated in terms of a disorder of polysynaptic dopaminergic circuits, between prefrontal and striate centres. Wender's notion of a disorder of reinforcement is broadened to include a disorder of planning and correction of behaviour, including capacity for cortical control of automatic instinctual motor programmes. The dopamine hypothesis of Attention Deficit Hyperactivity Disorder (ADHD) is examined from the point of view of differential dose effects of CNS stimulant medications, and theories of neural control. Clinical, animal and neurophar-macological studies are reviewed. Implications of the findings for understanding clinical and side effects in ADHD children of stimulants are discussed.