Two of the hypotheses on regional brain dysfunction in schizophrenia that have received some support in studies of cerebral blood flow (CBF) and cerebral metabolic rate (CMR) are: (1) left hemispheric dysfunction and overactivation (laterality) and (2) frontal lobe deactivation or failure to activate (frontality). Although these hypotheses are not mutually exclusive, their relative importance for providing clues to neural underpinnings of symptoms specific to schizophrenia depends on their ability to predict variation in symptomatology. A potentially efficient strategy for such study is to start with physiological parameters of laterality and frontality, and correlate them with measures of severity of clinical symptoms specific to schizophrenia. For two schizophrenic samples reported earlier, we derived laterality (left-right hemispheres) and frontality (frontal-posterior regions) measures of CBF (Study 1) and CMR (Study 2), and correlated them with symptom specificity, defined as the difference in severity of symptoms specific and nonspecific to schizophrenia assessed by the Brief Psychiatric Rating Scale. In both studies, low but significant positive correlations were obtained between the specificity score and laterality for CBF in Study 1 and for CMR in Study 2, but not frontality. The results suggest that in these samples disturbances in lateralized activity are more prominently associated with the phenomenology of schizophrenia than disturbed frontal lobe activity.