The absence of an animal model that accurately approximates schizophrenia limits current research into the pathophysiology of this disorder. Obviously, the cognitive disturbances associated with schizophrenia are difficult to evaluate in laboratory animals. Nonetheless, animal studies have provided insight into the anatomy and physiology of the brain systems that have been implicated in schizophrenia. These studies also suggest how brain systems may be involved in information processing in normal and pathological conditions. Thus, a careful assessment of the properties and functions of the brain regions suggested to be involved in schizophrenic symptoms has been a primary objective in several laboratories. In this review, we discuss the interactions among the brain regions implicated in schizophrenia-the ventral striatum, prefrontal cortex, hippocampus, and dopamine systems-and provide an integrative model linking altered function in these regions with specific clusters of symptoms of schizophrenia.Key words: Nucleus accumbens, hippocampus, prefrontal cortex, thalamus, dopamine, negative symptoms, positive symptoms, thought disorder. Schizophrenia Bulletin, 24(2):267-283,1998.Schizophrenia is a complex disorder characterized by a profound disturbance of cognitive functions. A major problem in the study of schizophrenia is the diversity of its symptoms, leading to the suggestion that schizophrenia is actually a cluster of diseases. An integrative clinical view was brought up by Liddle, who used factor analysis to segregate symptoms of schizophrenia into three clusters-reality distortion, psychomotor poverty, and disorganization (Liddle et al. 1992fc)-and proposed that dysfunctions in specific brain regions were involved in each cluster of symptoms (Liddle et al. 1992a). This interpretation is reinforced by a number of studies that implicate a variety of structures in the pathophysiology of schizophrenia. These structures include the prefrontal cortex (PFC), medial temporal lobe (including the hippocampus), ventral striatum, and mesolimbic dopamine (DA) system. In this review, we will link information regarding the physiological interactions among these systems with clinical investigations, in an attempt to analyze these symptom clusters from an anatomical perspective.