OBJECTIVE: Glutamate and glutamine were examined in vivo in nonpsychotic adolescents at high genetic risk for schizophrenia by using 3-T proton magnetic resonance spectroscopy (1H-MRS). METHOD: Spectra from the right medial frontal lobe of 20 adolescents who had a parent with schizophrenia (high-risk group; mean age=16.4 years) were compared with spectra obtained from adolescent offspring of parents with no history of schizophrenia (low-risk group; mean age=16.7 years). RESULTS: Glutamate/glutamine was significantly higher in the adolescents at high genetic risk for schizophrenia than in the low-risk offspring. Age, premorbid adjustment scale scores, and other 1H-MRS metabolites did not differ between groups. Global Assessment of Functioning Scale scores and socioeconomic status were lower in the high-risk group. DISCUSSION: The finding of glutamate/glutamine abnormalities in a group of subjects at high genetic risk for schizophrenia lends support for both the glutamate dysfunction and neurodevelopmental hypotheses for schizophrenia.