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Background Depression during pregnancy has been demonstrated to be predictive of low birthweight, prematurity, and postpartum depression. These adverse outcomes potentially have lasting effects on maternal and child well-being. Socio-economically disadvantaged women are twice as likely as middle-class women to meet diagnostic criteria for antenatal major depression (MDD), but have proven difficult to engage and retain in treatment. Collaborative care treatment models for depression have not been evaluated for racially/ethnically diverse, pregnant women on Medicaid receiving care in a public health system. This paper describes the design, methodology, culturally relevant enhancements, and implementation of a randomized controlled trial of depression care management compared to public health Maternity Support Services (MSS). Methods Pregnant, public health patients, > 18 years with a likely diagnosis of MDD or dysthymia, measured respectively by the Patient Health Questionnaire-9 (PHQ-9) or the Mini-International Neuropsychiatric Interview (MINI), were randomized to the intervention or to public health MSS. The primary outcome was reduction in depression severity from baseline during pregnancy to 18-months post-baseline (one-year postpartum). Baseline results 168 women with likely MDD (96.4%) and/or dysthymia (24.4%) were randomized. Average age was 27.6 years and gestational age was 22.4 weeks; 58.3% racial/ethnic minority; 71.4% unmarried; 22% no high school degree/GED; 65.3% unemployed; 42.1% making < $10,000 annually; 80.4% having recurrent depression; 64.6% PTSD, and 72% unplanned pregnancy. Conclusions A collaborative care team, including a psychiatrist, psychologist, project manager, and 3 social workers, met weekly, collaborated with the patients' obstetrics providers, and monitored depression severity using an electronic tracking system. Potential sustainability of the intervention within a public health system requires further study. [ABSTRACT FROM AUTHOR]