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Significant levels of prenatal depression are reported from the Indian subcontinent (25–45%). A wide variety of measures have been used to screen for prenatal depression in western research. However, little evidence exists on the use of such measures in the context of the developing world. The objective of this study was to assess the validity of the Edinburgh Postnatal Depression Scale (EPDS) and the Kessler 10 Scale of Psychological Distress (K10) as screening measures for prenatal depression in rural South India. One hundred ninety-four women in their third trimester of pregnancy were assessed at a rural prenatal clinic in Karnataka, South India, using the EPDS, the K10 (scored 0–40) and a structured diagnostic psychiatric interview to establish a DSM-IV diagnosis of depression. Depressed women scored significantly higher on the EPDS and K-10 than controls. A receiver-operating characteristic analyses showed both scales to be good screening instruments for prenatal depression in rural South India at a cut-off of ≥13 on the EPDS (sensitivity = 100%, specificity = 84.90%, and area under the curve = 0.95) and ≥6 on the K10 (sensitivity = 100%, specificity = 81.30%, and area under the curve = 0.95). The EPDS and K10 have thus been shown to have equally good sensitivity and specificity in rural settings in the developing world at a cut-off score of ≥13 and ≥6, respectively. This study demonstrates the validity of the EPDS and K10 in screening pregnant women for depression during their prenatal check-ups.