Depression increases sharply during adolescence. This study prospectively investigated etiological predictions from the hopelessness theory of depression (Abramson, Metalsky, & Alloy, 1989) among a sample of middle to late adolescents to examine whether this theory can be applied to this important age group. High school students completed measures of attributional style, hopelessness, negative stressors, general depressive symptoms, and specific hypothesized hopelessness depressive (HD) symptoms at two rimes separated by 5 weeks. Results showed that the attributional style X stress interaction predicted increases in depressive symptoms from TI to T2. Gender moderated this interaction for the BDI such that the vulnerability-stress component held for boys, bur not girls. Consistent with the vulnerability-stress component of the theory, these effects held for the increase in HD symptoms for both boys and girls, but not non-HD symptoms. Mediational analyses did not provide consistent support for hopelessness as a mediator of this association. These results were mostly the same whether the internal, stable, and global dimensions versus only the stable, global dimensions of attributional style were used to operationalize cognitive vulnerability. Overall, results suggest that the cognitive vulnerability-stress aspect of the hopelessness theory can be applied to middle to late adolescence.