Although the prognostic significance of depression and hostility has been established, little is known about how they operate together to influence disease processes. This study explored the independent and interactive relationships between these constructs and the expression of inflammatory markers implicated in the pathogenesis of coronary heart disease. One hundred adults completed measures of cynical hostility and depressive symptoms, and had blood drawn to assess serum levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α. Depression was directly related to inflammatory markers, but hostility was not. A significant interaction between hostility and depression emerged. Among participants scoring low in depressive symptoms, hostility was positively associated with interleukin-6 and tumor necrosis factor-α concentrations. Hostility's association with these inflammatory markers was much weaker among participants with moderate depressive symptoms, however, and virtually nil among participants with severe depressive symptoms. Neither depression nor hostility was associated with interleukin-1β concentrations. These findings highlight the importance of considering both the independent and interactive relationships among psychosocial characteristics involved in disease.