Clinical trials in patients with congestive heart failure have shown a wide disparity in the hemodynamic responses to chronic therapy with newer positive inotropic drugs. Therefore, the long-term efficacy of enoximone was studied in 10 patients with severe congestive heart failure. Patients were evaluated clinically, left ventricular dimensions and contractile state were assessed by echocardiography, and exercise testing was performed at basic conditions and after 1 and 8 weeks of enoximone treatment with a daily dose between 150-300 mg. Previous therapy of heart failure was continued during the study period. Clinical symptoms of eight patients were improved after 1 week and six patients showed sustained improvement after 8 weeks of enoximone treatment. The administration of enoximone increased ejection fraction by about 25% after 1 week with a similar response after 8 weeks. Five of six patients who were able to perform exercise testing initially experienced an increased exercise capacity over the study period. The enoximone regimen was continued in the responders; after 1 year, data on three patients are available and show sustained efficacy of enoximone treatment in two patients. The administration of the drug was well tolerated without any deterioration of arrhythmias. There is evidence that oral enoximone treatment may be useful as additional therapy in patients with severe heart failure.