OBJECTIVE: Abnormalities in frontal lobe phosphorous metabolism in patients with bipolar disorder have been reported, but many of the patients studied were receiving lithium. In this study, medication-free bipolar patients were examined to determine abnormalities in frontal lobe high-energy phosphorous metabolism. METHOD: In vivo phosphorous-31 magnetic resonance spectroscopic imaging was performed on 12 unmedicated, euthymic bipolar patients and 16 healthy comparison subjects. The percentages of total phosphorous signal for phosphomonoesters, inorganic phosphate, phosphodiesters, phosphocreatine, and beta-ATP were calculated. RESULTS: In relation to the comparison group, the patients with bipolar disorder had significantly lower phosphomonoester values and higher phosphodiester values in both the left and right frontal lobes. The patients also had a significantly higher right-to-left ratio of frontal lobe phosphocreatine. No other differences in phosphorous metabolites or lateralized asymmetries were noted. CONCLUSIONS: This preliminary study provides support for abnormal frontal lobe phosphorous metabolism in bipolar disorder.