Many studies have documented the negative effects of depression on adherence to recommended treatment; however, little is known about the mechanism underlying this relationship. Using the Kenny and Baron analytic framework of mediation, the authors assessed whether self-efficacy mediated the relationship between depression and medication adherence in 167 hypertensive African Americans followed in a primary care practice. Depressive symptoms are associated with poor medication adherence (beta=.013, p=.036) and low self-efficacy (beta=-.008, p=.023). Self-efficacy is negatively associated with medication adherence at follow-up (beta=-.612, p<.001). The relationship between depressive symptoms and medication adherence becomes nonsignificant when controlling for self-efficacy (beta=.010, p=.087). Implications for further examination into the mediating role of self-efficacy and the deleterious effect of depression on medication adherence are discussed.