Beta-adrenergic blockade represents a promising therapeutic approach to idiopathic dilated cardiomyopathy. Bucindolol, a new beta-blocker, showed favorable effects in a short-term (3 month) trial in idiopathic dilated cardiomyopathy. To assess long-term response, 20 study patients (7 of 9 patients previously assigned to the placebo group and 13 of 14 patients previously assigned to bucindolol therapy) received long-term bucindolol therapy and were followed up for a mean of 23 ± 4 months (range 17 to 30). The mean patient age was 49 years (range 29 to 66) and the median duration of disease was 11 months (range 1 to 190). Ten patients were in functional class II and 10 were in class III; 15 patients were men. At the end of the common follow-up time, all 20 patients were alive, 17 continued to receive bucindolol (mean dose 176 mg/day, range 25 to 200), and 2 underwent cardiac transplantation. Left ventricular ejection fraction increased from a baseline value of 25 ± 8% to 35 ± 13% (n = 19 pairs, p < 0.001). Functional class improved in 12, was unchanged in 5 and deteriorated in 3 (p = 0.056). Exercise time was maintained (9.4 ± 3.1 versus 9.1 ± 3.5 min, n = 19, p = NS), as was maximal oxygen uptake (19.2 ± 4.9 versus 18.8 ± 5.7 ml/kg per min, n = 19, p = NS). Thus, long-term bucindolol therapy leads to substantial increases in ejection fraction and to improved functional class while stable exercise performance is maintained. Also, similar or better ejection fractions and exercise times were observed after long-term compared with short-term (3 months) therapy. Given these excellent results with respect to drug tolerance, survival rate and functional efficacy after approximately 2 years, long-term bucindolol therapy deserves further evaluation in patients with heart failure, especially those with idiopathic dilated cardiomyopathy who are in functional classes II and III.