Background: Large community based epidemiological surveys have consistently identified high co-morbidity between major depressive episode (MDE) and generalized anxiety disorder (GAD). Some have suggested that this co-morbidity may be artificial and the product of the current diagnostic system. Due to the added direct and indirect costs associated with co-morbidity it is important to investigate if methods of diagnostic classification are artificially increasing the level of observed co-morbidity. Methods: The item response theory log-likelihood ratio procedure was used to test for differential item functioning of MDE symptoms between respondents with and without a diagnosis of GAD in the 2001-2002 National Epidemiological Survey on Alcohol and Related Conditions. Results: The presence of GAD significantly increased the chances of reporting any symptom of MDE with odds ratios ranging from 2.54 to 3.60. However, there was no indication of significant differential item functioning of MDE symptoms in respondents with and without GAD. Conclusions: The lack of any significant differential item functioning indicates that cases with GAD do not present with a distinct MDE symptom profile, one that is consistent with the endorsement of symptoms that are conceptually similar in nature between the two disorders, compared to cases without GAD. This does not support the hypothesis that co-morbidity between MDE and GAD is artificially inflated due to similar symptom criteria required by the current diagnostic system. Instead, MDE and GAD may be thought of as two distinct diagnostic entities that frequently co-occur due to a shared underlying trait.