Frontal lobe dysfunction has been linked to negative symptoms of schizophrenia. We used phosphorus-31 magnetic resonance spectroscopy (31P-MRS) to examine phosphorous metabolism in frontal brain regions in 26 schizophrenic patients compared with 26 sex- and age-matched control subjects. The relative signal intensities of phosphorous metabolites in frontal regions did not differ significantly between schizophrenic patients and control subjects. However, phosphomonoester levels were significantly decreased in frontal regions of 12 schizophrenic patients who had high scores on negative symptom subscales from the Brief Psychiatric Rating Scale (i.e., emotional withdrawal, motor retardation, and blunted affect) compared with 14 patients with low negative symptom scores on the same subscales and control subjects. The correlations between negative symptoms and phosphorous metabolism in the frontal lobes support the "hypofrontality hypothesis" in schizophrenia.