The antipsychotic effects of dopaminergic antagonists suggest dopaminergic hyperactivity plays a role in schizophrenia.4,6,23,29 However, an elevated number of D-2 dopamine receptors in the left putamen of nontreated schizophrenics has been reported12 which is consistent with a diminution of dopaminergic transmission in the ventral striatum. Morphological and functional studies have shown marked alterations in the left medial temporal lobe (entorhinal cortex, hippocampus, parahippocampus gyrus) of schizophrenics.3,7,8,10,11,34,35 As the entorhinal cortex and the ventral hippocampus project to the ventral striatum,14,18,30,33,36 the functional relationship between left temporal structures and the left ventral striatum may be impaired in schizophrenics. To assess the validity of this hypothesis, we investigated the existence of a preferentially left hemispheric interdependency between dopaminergic pathways in male rats. We found that dopaminergic projections in the entorhinal cortex and the ventral hippocampus regulate dopaminergic transmission in the nucleus accumbens, particularly in the left hemisphere. Temporal D-2 dopamine receptors seem to be primarily involved in this effect. This lateralized interdependent functioning appears structurally based. These results may provide new insights into the pathophysiology of schizophrenic psychoses.