The Internet may offer new opportunities for treating depressed adolescents. However, before such treatments are possible, well-validated screening instruments are needed. In the current study, we validate two Internet-based screening instruments for depression among adolescents, the major depression inventory (MDI), and the Center for Epidemiological Studies-Depression scale (CES-D). A total of 1,392 adolescents, recruited through high schools and the Internet, filled in the online questionnaires. Of these, 243 (17%) were interviewed with the MINI diagnostic interview to assess the presence of a mood disorder. Cronbach's alpha was high for both the CES-D (0.93) and the MDI (0.88), and both correlated highly with each other (0.88; P < .001). The scores on both instruments were significantly increased in all subjects with a mood disorder, whether current or lifetime, except for lifetime minor depression. In the ROC analyses, high areas under the curve were found for the MDI (0.89) and CES-D (0.90). The best cut-off point for the MDI was 19 (sensitivity: 90.48; specificity: 71.53), and for the CES-D it was 22 (sensitivity: 90.48; specificity: 74.31). We conclude that the MDI and CES-D are reliable and valid instruments that can be used for this screening.