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Postpartum depression affects approximately 13% of mothers but up to 50% of all cases of this tragic illness can go undetected.The purpose of this study was to compare the performance of a newly created instrument, the Postpartum Depression Screening Scale (PDSS), with the Edinburgh Postnatal Depression Scale (EPDS) and a general depression scale, the Beck Depression Inventory-II (BDI-II).In this methodological design a total of 150 new mothers completed these three instruments in random order, followed immediately by a DSM-IV diagnostic interview. Using the LABROC I program, the areas under each of the instrument’s Receiver Operator Characteristic (ROC) curves were compared to determine if they were significantly different.Eighteen (12%) of the women were diagnosed with major postpartum depression, 28 women (19%) with minor postpartum depression, and 104 women (69%) with no depression. Compared to the EPDS, the PDSS had a significantly larger area under the ROC curve when screening for major or minor postpartum depression. When using the published recommended cut-off scores for major depression for the three instruments, the PDSS achieved the highest combination of sensitivity, 94%, and specificity, 98%. When detecting women with major or minor postpartum depression, the PDSS again yielded the highest combination of sensitivity (91%) and specificity (72%) of the three instruments. The PDSS identified 17 (94%) of the women diagnosed with major postpartum depression, the EPDS identified 14 of these women (78%), and the BDI-II identified 10 of the 18 women (56%).If mothers identified as “most depressed” are substantially determined by the instrument used, the implications for both research and clinical practice are significant. Researchers and clinicians need to be aware of the differential sensitivity of depression instruments which, while supposedly measuring the same construct, are focused on different components of this mood disorder.