A frontostriatal hypothesis of schizophrenia is advanced which takes into account evidence from studies of neurochemical pathology, functional imaging, cognitive neuropsychology, and experimental and clinical psychopharmacology, in addition to factor analyses of the symptomatic heterogeneity of this disorder. This evidence is illuminated by the recent characterization of anatomically segregated, functionally distinct corticostriatal loops which provide possible substrates for understanding the significance of functional changes in striatal and cortical dopaminergic activity interacting with other forms of structural pathology in schizophrenia.