The association between marijuana use and depressive symptoms was examined longitudinally in a sample of 622 African American youth, interviewed on six occasions, using hierarchical linear modeling (HLM). We considered whether depressive symptoms predicted changes in marijuana use and vice versa from high school through the transition into young adulthood. We also examined gender differences in these behaviors over time. The results indicated that depressive symptoms predicted later marijuana use only for males. Marijuana use did not predict later depressive symptoms for females or males. These findings are consistent with a unidirectional hypothesis indicating that marijuana use may play a role as mood regulator among young males, but not among females. Research findings also indicate that females with lower depressive symptoms use more marijuana than females who report high depressive symptoms. These findings did not change even after controlling for the effects of using other substances at previous stages, school achievement, and demographics factors. These results suggest that depressive symptoms may be an antecedent of marijuana use among African American males.