The acute effects of an oral preparation of sulmazol, a recently synthesized cardiotonic agent, were assessed by means of a Swan-Ganz catheter in 10 patients who had advanced heart failure that persisted despite treatment with digitalis, diuretics and nitrates. All patients demonstrated a hemodynamic improvement. Pulmonary wedge pressure decreased significantly 1 h after administration from 26 ± 2 to 16 ± 3 mm Hg (mean ± SEM; 32%; p < 0.01) and this decrease remained significant at least 6 h after intake. The cardiac index increased from 1.8 ± 0.1 to 2.4 ± 0.1 l/min/m<sup>2</sup> (33%; p < 0.01) and remained significant up to 6 h later. Total systemic and pulmonary resistances were also significantly decreased (peak changes 28% and 46%, respectively) up to 6 h later. Heart rate and mean blood pressure were unaffected. Once the duration of action was assessed for each patient, a short-term oral therapy was initiated for 48 h. Hemodynamic measurements performed 24 h and 36 h following the commencement of this chronic therapy showed the sustained hemodynamic improvement. 7 patients were continued on sulmazol therapy for 3 weeks to 6 months. Side effects were nausea and vomiting (which were likely to be dose-related), worsening arrhythmias and a possible rebound phenomenon after withdrawal. Although orally administered sulmazol shows promise as a potentially useful agent in the treatment of advanced heart failure, the safety of this drug remains to be established.