This study examines an alternative to a narrow locus-of-dysfunction cortical pathophysiology in schizophrenia, which in turn suggests a modified approach to the analysis of data from regional cerebral blood flow studies. The results provide qualified support for a model of impaired differentiation of cortical activity in schizophrenia. As an index of the differentiation of cortical fields, regional gradients of cortical blood flow were examined. Medicated patients (n = 15) failed to show the differentiation of networks in frontal areas during a verbal memory recognition task observed in normal comparison subjects (n = 15). Unmedicated patients (n = 15) at rest tended to lose normal lateralization and had increased gradients in the right frontal area compared with normal comparison subjects.