Fourteen patients with moderately severe congestive heart failure (CHF) were given clonidine orally (0.2 and 0.4 mg doses) to determine the hemodynamic effects of a typical centrally acting vasodilator. The 0.2 mg dose significantly reduced mean systemic (15%) and mean pulmonary artery (20%) pressure; the corresponding reductions in vascular resistance were not as great because of a diminished cardiac output. Pulmonary capillary wedge pressure decreased significantly (27%). Heart rate decreased 11% and stroke volume remained unchanged. At a higher dose (0.4 mg), clonidine augmented these reductions but increased stroke volume modestly (15%). Isovolumic developed pressure/duration of isovolumic contraction and the duration of the preejection period were used as indexes of inotropy. After both doses, isovolumic developed pressure/duration of isovolumic contraction decreased dramatically (greater than or equal to 33%) and the preejection period increased substantially (greater than or equal to 18%) (both p less than 0.05). Compared with currently employed vasodilating agents, the centrally acting agent clonidine appears unique in that the drug-induced systemic and pulmonary arterial vasodilation are not accompanied by a commensurate improvement in ventricular systolic function. This lack of improvement appears to be a result of negative inotropic effects.