The CIDI Short Form is a brief survey instrument designed to identify episodes of major depression. The instrument was developed for inclusion in the US National Health Interview Survey, but has also been used in the Canadian National Population Health Survey (NPHS). In this study, data deriving from use of the CIDI Short Form in the NPHS are compared to published data from the Mental Health Supplement of the Ontario Health Survey, which utilized a fully validated structured interview: the Composite International Diagnostic Interview (CIDI). In an additional analysis, the sensitivity and specificity of the Short Form were evaluated in relation to the full CIDI mood disorders section in a clinical sample of 122 psychiatric in-patients. Relative to published data from the Ontario Health Survey, application of the CIDI Short Form in the NPHS resulted in an overestimation of major depression prevalence by approximately 50%. In the clinical sample, the CIDI Short Form was highly sensitive (98.4%), but not highly specific (72.7%). Active medical conditions, substance use disorders and dysthymia were frequently observed among subjects with false positive CIDI Short Form ratings. The CIDI Short Form appears to overestimate the 12-month period prevalence of major depression when it is applied in community samples. Since the Short Form does not make exclusions for organically induced symptoms, it is probable that some subjects with depressive symptoms secondary to physical illnesses and/or drug exposures score above the instrument's threshold, perhaps leading to an elevation in period prevalence rates.