The original dopamine hypothesis stated that schizophrenia is the result of increased activity of dopamine in the basal ganglia. This hypothesis was based on the mode of action of neuroleptics and the finding that dopamine agonists worsened psychotic symptoms in schizophrenic patients. Recent evidence suggests the role of dopamine in schizophrenia to be more complicated: it appears to be decreased in the prefrontal cortical areas and increased in the mesocortical pathways. Moreover, it has become evident that serotonergic systems may be important in schizophrenia as well. This has been based on challenge studies and the mode of action of a typical neuroleptics. However, it is unlikely that schizophrenia is either serotonergic or dopaminergic in nature. It is more likely that there is a dysfunction in the interaction between these two neurotransmitter systems. If so, this would be quite important for the development of new neuroleptics. Drugs that would block dopamine and serotonin systems may induce less side effects and be more effective in reducing negative symptoms. Indeed, it appears likely that such compounds will radically change the treatment of schizophrenic patients.