In vivo proton magnetic resonance spectroscopy ((1)H MRS) was used to study possible neurochemical abnormalities in drug-free, symptomatic panic disorder patients at rest. (1)H MRS was performed in 11 panic disorder patients and 11 healthy age- and sex-matched comparison subjects. Levels of brain metabolites were determined in the right medial temporal lobe region (encompassing the whole amygdala and part of the hippocampus) and in the medial prefrontal cortex on the basis of previous work with both structural and functional neuroimaging techniques. The concentration of creatine and phosphocreatine, metabolites involved in energy-dependent systems in brain, was significantly lower in the right medial temporal lobe region of panic disorder patients compared to healthy subjects. No significant differences between the two groups were observed in the medial prefrontal cortex. These results provide neurochemical evidence suggesting the involvement of the amygdalohippocampal region in the pathogenesis of panic disorder.