Converging evidence from animal research and human brain imaging studies, points to an important role of cortical-striatal motor circuitry in the incidental learning of serial order information. To date, attempts to address this role through the study of patients with striatal disorder have proved inconclusive. The present study examined the impact of a therapeutic lesion of the globus pallidus in patients with Parkinson's disease. The lesion, which blocks a primary output of the putamen to the motor cortices, eliminated incidental learning relative both to controls and unoperated patients. The finding offers support for models proposing that context detection within the striatum is a central process in serial order learning. An unexpected effect of the lesion was to significantly reduce the response time to random stimuli relative to an ordered series, the opposite of the normal pattern. It is speculated that this may reflect an unconscious alerting response to novelty, a process suggested to involve the ventral striatum and its cortical targets. Research on Parkinson's disease patients undergoing functional basal ganglia surgery may shed further light on the mechanisms and neuronal substrate of serial order learning in humans. Copyright 2003 Lippincott Williams & Wilkins