To determine the respective contribution of the subcortical structures and the prefrontal cortex in behavioural adaptation, we applied the delayed response paradigm, considered as a functional marker of the dorsolateral region of the prefrontal cortex, to patients with striatal dysfunction: Parkinson's disease (n = 27), progressive supranuclear palsy (n = 20); to patients with prefrontal lesions (n = 10) and to normal control subjects (n = 24). The performance of each group was compared in four experiments: a delayed response task in which the correct answer was previously indicated by an explicit cue (externally guided task); delayed alternation and non-alternation tasks coupled with a delayed reversal task in which the patient had to discover the rule by himself in the absence of explicit cues (internally driven tasks). All groups of patients showed a short-term spatial representational memory deficit in the externally guided situation. Patients with striatal dysfunction showed difficulties in re-engaging attention on a new programme and in maintaining it. However, they did not express the spontaneous tendency to alternate nor the severe difficulties in disengaging from a previous pattern of response demonstrated by patients with prefrontal lesions. These results validate the concept of a striato-frontal functional system in humans and suggest the existence of two different levels of behavioural organization: elaboration of new programmes of behaviour in association with inhibition of previously established ones, that might be under frontal lobe control; maintenance of the new programme until the action has been accomplished and automatization for a routine utilization, that might be under control of the striatum.