We studied 18 never-medicated schizophrenic patients and 22 normal control subjects with 18F-deoxyglucose (FDG) positron emission tomography. Patients and controls performed the continuous performance test during FDG uptake. Cortical and subcortical structures comprising two circuits selected on the basis of several theoretical models of schizophrenia were examined. The correlation of glucose metabolic rate (GMR) for each structure in each circuit with connected structures was calculated and tested for two-tailed significance. Schizophrenics showed significantly different patterns of intercorrela-tions for both circuits. The largest difference was in the correlation of GMR in the anterior thalamus with the frontal cortex, a key element in the thalamo-cortical-striatal circuit suggested to be abnormal in some models of schizophrenia. Correlations of the frontal lobe with other regions were also more positive in normal controls than schizophrenics; controls had three correlational paths from the frontal cortex (to temporal cortex, ventral anterior thalamus, and dorsal medial thalamus) with significantly more positive correlations than schizophrenics, perhaps consistent with other findings of frontal cortical dysfunction in schizophrenia. Normal controls also had both more significant positive and more significant negative correlations between the occipital cortex and other brain areas than schizophrenics. Correlations between homologous areas in the right and left hemispheres were prominent in both groups.