The efficacy of flosequinan 100 mg once daily was evaluated in 15 patients with severe congestive heart failure (New York Heart Association [NYHA] class II-IV) who had not responded adequately to digoxin and diuretics. Efficacy assessments using non-invasive techniques included exercise capacity, haemodynamics and left ventricular function. Determinations were made after 3 and 21 days' treatment, and compared with baseline. Flosequinan significantly increased exercise capacity by 27% after 3 days (+79 seconds, p = 0.015) and by 43% after 21 days (+123 seconds, p = 0.0007) and was accompanied by an increase in heart rate (+7.2 beats/min, p = 0.03; +9.1 beats/min, p = 0.03, respectively). Cardiac index and cardiac output were also significantly increased but only after 21 days' treatment (+0.3 l/min/m2, +16% and +0.5 l/min, +14%, respectively; both p = 0.008). Flosequinan was well tolerated, with headache being the most frequently reported adverse event and only 1 patient being withdrawn. One patient died but this was not unexpected in a group of patients with severe heart failure. Using non-invasive techniques this study demonstrated that in patients with severe chronic congestive heart failure, flosequinan increased exercise capacity and cardiac output, the latter being achieved mainly by an increase in heart rate.