To determine whether tumor necrosis factor-α (TNFα) has a negative inotropic effect on the adult heart, the effects of TNFα on the left ventricle and isolated adult cardiocytes were investigated. Studies in the Langendorff heart and isolated adult cardiac myocytes showed that TNFα has a concentration-and time-dependent negative inotropic effect, and that this effect is fully reversible after the removal of TNFα. The time to the onset of the TNFα-induced negative inotropic effects was 15-20 min, and the TNFα concentration was found to be 90-100 U/ml in the Langendorff heart and the isolated cardiac myocytes. Treatment with neutralizing anti-TNFα antibody prevented the negative inotropic effect of TNFα in isolated myocytes. The present results of the study indicate that TNFα has a direct negative inotropic effect on both the intact heart and adult cardiac myocytes.