This study examined the factorial invariance of the Center for Epidemiologic Studies of Depression Scale (CES-D) across gender and time during adolescence. The factor structure of the CES-D was compared at four annual measurement waves in a community sample of 2650 Australian adolescents. Confirmatory factor analyses showed that the factor structure of the CES-D was generally invariant across gender and time. However, gender differences were found on three items: for all waves the item 'I had crying spells' was a stronger indicator for depressive affect in females than males. On the final three waves the item 'people were unfriendly' loaded significantly higher on the factor 'Interpersonal Relations' for males than females. On Wave 2 and 3 males interpreted the item 'everything I did was an effort' with a positive connotation, whereas females interpret it with a negative association. These gender-differences are discussed from both a theoretical and a methodological perspective.