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Two analytical methods for assessing regional glucography with positron emission tomography were compared in 16 patients with schizophrenia and 11 patients with affective disorders. Patients were off all medication a minimum of 14 days and an average of 39.8 days. The subjects were administered fluorine-18-labeled 2-deoxyglucose just before receiving a 34-minute one-per-second series of unpleasant electrical stimuli to their right forearm while resting with their eyes closed in a darkened, acoustically attenuated psychophysiological testing chamber. Following monitored stimulation in the controlled environment, the subjects were scanned and the images were converted to values of glucose use in micromoles per 100 grams per minute, according to Sokoloff's model. Data were analyzed by a four-way analysis of variance (ANOVA) for independent groups (normal subjects, schizophrenic patients, and patients with affective disorders) and for repeated measures of slice level (supraventricular, midventricular , and infraventricular ), hemisphere (right, left), and anteroposterior position (four sectors). Normal individuals and patient groups both showed a significant anteroposterior gradient in glucose use, with the highest values in the sector farthest to the front. Patients with schizophrenia and those with affective illnesses showed less of an anteroposterior gradient than normal individuals, especially at superior levels, which was statistically confirmed by ANOVA. Neither the group differences in whole-brain glucose use nor the left-right asymmetries reached statistical significance. A second technique, involving reconstruction of the lateral cortical surface, also revealed differences between schizophrenics and normal individuals in the superior frontal cortex. These results are consistent with our earlier reports of a relative hypofrontal function in schizophrenia compared with controls; they also extend the finding to the affective illnesses, the other group of major psychoses.