Despite the common use of the 12-item General Health Questionnaire (GHQ-12) with adolescents, there is limited data supporting its validity with this population. The aims of the study were to investigate the psychometric properties of the GHQ-12 among high school students, to validate the GHQ-12 against the gold standard of a diagnostic interview, and to suggest a threshold score for detecting depressive and anxiety disorders. Six hundred and fifty-four high school students from years 10 to 12 (ages 15-18) completed the GHQ-12 (Likert scored) and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-IV-Test Revision (DSM-IV-TR). Receiver operating characteristic (ROC) curves were plotted. The mean GHQ-12 score for the total sample was 9.9 (S.D.=5.4). Results from the ROC curve indicated that the GHQ-12 performed better than chance at identifying depressive and anxiety disorders (area under the curve (AUC)=0.781). A GHQ-12 threshold score of 9/10 for males and 10/11 for females was found to be optimal. Given the significant proportion of mental illness among high school students, there may be a need to introduce screening for mental illnesses as part of the school curriculum. This can assist with the early identification and enable low stigma preventive intervention within the school environment. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.