Vesnarinone, a recently synthesized quinolinone derivative with positive inotropic properties, has been reported to improve survival of patients with congestive heart failure. However, the mechanisms that contribute to the increased survival are unknown. In this study, we showed vesnarinone had inhibitory effects on the production of tumor necrosis factor-alpha, interferon-gamma, interleukin-1 beta and interleukin-2 by stimulated human peripheral blood mononuclear cells, human Jurkat T cell line and THP-1 monocytic cell line. Vesnarinone may exert its beneficial effect on patients with congestive heart failure, in part, by its immunomodulating activity.