Despite the proven efficacy of acute and maintenance pharmacotherapy in schizophrenia, practical methods for identifying patients who require continuous treatment to prevent relapse have not been established. We hypothesized that a pathologic overactivity of mesolimbic and mesocortical dopamine neural systems, that mediates positive psychotic symptoms in the acute phase of the illness, persists in some outpatients who are vulnerable to relapse despite appearing clinically stable. To test and determine if putative measures of central nervous system dopamine activity predict outcome, 41 stable outpatients receiving neuroleptic maintenance treatment underwent provocative tests with methylphenidate in a randomized double-blind placebo controlled design in which behavioral, neuromotor, biochemical, and cardiovascular responses were measured. Patients were then withdrawn from medication and monitored for 52 weeks, or until relapse. The results indicate that psychotic symptoms and their activation by methylphenidate, and the presence of tardive dyskinesia are associated with each other and with a higher risk of relapse. These findings partially support our hypothesis and offer potentially useful measures for the identification of candidates for reduced dose neuroleptic maintenance treatment strategies in schizophrenia.