The purpose of this study was to examine the relation between maternal depressive symptoms and spontaneous preterm birth. From 1991 to 1993, pregnant, African-American women were prospectively enrolled at four hospital-based clinics in Baltimore, Maryland, that serve low-income areas of the city. The Center for Epidemiologic Studies Depression (CES-D) Scale was used to assess depressive symptoms. Multiple logistic regression analysis estimated the independent contribution of maternal depressive symptoms to spontaneous preterm birth, controlling for behavioral, clinical, and demographic variables. Among the 1,399 women in the sample, 117 (8.4%) had a spontaneous preterm delivery. Spontaneous preterm birth occurred among 12.7% of those with a CES-D score in the upper 10th percentile and among 8.0% of those with a lower score (relative risk = 1.59). The adjusted odds ratio for an elevated CES-D score was 1.96 (95% confidence interval: 1.04, 3.72); hence, maternal depressive symptoms in this sample of African-American women were independently associated with spontaneous preterm birth. Effective treatment of depression in pregnant women could ultimately result in a reduction of spontaneous preterm births.