The safety and efficacy of long-term oral piroximone therapy was assessed in 12 patients with chronic heart failure. Of these 12 patients, two died suddenly, and a further two were withdrawn because of worsening heart failure within 6 months while 8 completed the 1-year follow-up period. In 7 of these 8 patients, clinical evaluations showed sustained benefit, as demonstrated by significant increases in exercise tolerance. The remaining patient experienced a recurrence of severe heart failure at the end of follow-up. Twenty-four hour ambulatory electrocardiograms were compared in 9 patients before and during piroximone therapy. Aggravation of existing arrhythmias was observed in 3 patients, an amelioration in one with no change in the remaining 5. In the 5 patients in whom the hemodynamic effects of a single oral dose of 25 mg of piroximone were studied, the first dose resulted in a 20% increase in mean cardiac index and a 30% decrease in mean pulmonary capillary wedge pressure. This responsiveness to single-dose administration was maintained after 1-year follow-up. Likewise, comparison of the hemodynamic effects of four intravenous doses of piroximone revealed no significant difference in the response (n = 7), although the effects tended to be less marked at the end of follow-up. The present results suggesting that piroximone is effective and safe as adjunctive therapy in the management of patients with chronic heart failure will need to be confirmed in longer controlled trials.