Objective: The objective of this study was to evaluate a depression-focused treatment for smoking cessation in pregnant women versus a time and contact health education control. We hypothesized that the depression-focused treatment would lead to improved abstinence and reduced depressive symptoms among women with high levels of depressive symptomatology. No significant main effects of treatment were hypothesized. Method: Pregnant smokers (N = 257) were randomly assigned to a 10-week, intensive, depression-focused intervention (cognitive behavioral analysis system of psychotherapy; CBASP) or to a time and contact control focused on health and wellness (HW); both included equivalent amounts of behavioral and motivational smoking cessation counseling. Of the sample, 54% were African American, and 37% met criteria for major depression. Mean age was 25 years (SD = 5.9), and women averaged 19.5 weeks (SD = 8.5) gestation at study entry. We measured symptoms of depression using the Center for Epidemiological Studies-Depression Scale (Radloff, 1977). Results: At 6 months posttreatment, women with higher levels of baseline depressive symptoms treated with CBASP were abstinent significantly more often, F(1, 253) = 5.61, p = 0.02, and had less depression, F(1, 2620) = 10.49, p = 0.001, than those treated with HW; those with low baseline depression fared better in HW. Differences in abstinence were not retained at 6 months postpartum. Conclusions: The results suggest that pregnant women with high levels of depressive symptoms may benefit from a depression-focused treatment in terms of improved abstinence and depressive symptoms, both of which could have a combined positive effect on maternal and child health. (Contains 2 tables and 2 figures.)