Central neurophysiology can be measured with PET. These measurements are providing insights into the regional abnormalities associated with schizophrenia. Cohorts of schizophrenic subjects have been studied cross-sectionally in attempts to identify common regional deficits. More recently the advent of fast dynamic measurements of regional cerebral blood flow have allowed rapid serial measurements in the same subject in different brain states (activation studies). These complementary approaches are based upon, and are interpreted with reference to, a number of methodological considerations and underlying hypotheses. The key hypotheses underpinning cross-sectional and activation studies are discussed within the framework of the lesion model and functional anatomy models of brain function. This brief review of some assumptions, ideas and methodological constraints is illustrated with empirical data implicating the dorsolateral prefrontal cortex in schizophrenic symptoms.