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The US Preventive Services Task Force (USPSTF) has recommended depression screening for adults. Screening mothers has special importance to pediatricians because of the impact of maternal depression on children. The two screening questions endorsed by the USPSTF may allow pediatricians to screen mothers during routine well child care. This study explores the feasibility and yield of interview- and paper-based pediatric screening for maternal depression during well child visits. A structured interview script was developed to inquire about maternal depression. It included the two-question screen and required less than 1 minute to administer. An alternative paper-based screen asked the two questions after a brief written introduction providing the rationale. Four community pediatric practices in New Hampshire and Maine were trained in both screening approaches and developed plans on how to respond to positive screens (either question positive). The 11 providers at these sites tested the two approaches on two different series of mothers at well child visits. The pediatricians also reported barriers to the screening inquiries, maternal responses, and subsequent clinician actions and referrals. The pediatricians screened 250 mothers via the scripted interview. In a second trial, 223 women had paper-based depression screening. Yields from the paper-based screen were 22.9% versus 5.7% for the interview-based screener. Pediatricians also took on the new role of discussion of possible depression in about two thirds of cases. Subsequently, 7.6% of all women with paper-based screening were referred to mental health versus 1.6% with the interview-based screening. With the interview, mothers of children younger than 1 year of age were less likely to screen positive than those with older children (1.9% vs. 8.5%, p = .04). With the paper-based screener, no age differences in positive screen rates occurred. While both approaches to screening were feasible in primary care, the yield from the two different approaches differed substantially. This finding deserves exploration in future studies. With either of these screening approaches, pediatricians could enhance their detection of mothers at risk of depression. The outcomes of pediatrician screening and the best approach to follow-up care still need to be determined.