Cardiopulmonary exercise testing includes the monitoring of respiratory gases and airflow to determine oxygen uptake, carbon dioxide (CO2) production, respiratory rate, tidal volume, and minute ventilation during a graded maximal exercise test. A plateau in oxygen uptake, which occurs despite an increase in work load, and which is termed maximal oxygen uptake (VO2 max), correlates with the maximal exercise cardiac output and can therefore be used to grade the severity of heart failure. The anaerobic threshold occurs at 60 to 70% of VO2 max and is another indicator of the severity of heart failure and, when attained, indicates that the patient is close to performing a maximal test. We have found VO2 max and anaerobic threshold to be objective measures of efficacy of both investigational and noninvestigational therapy in patients with heart failure. A pulmonary limitation to exercise can be identified by the failure to attain anaerobic threshold or VO2 max, as well as exhaustion of the ventilatory reserve, as estimated by maximal voluntary ventilation. Thus, cardiopulmonary exercise testing can be used to (1) grade the severity of heart failure, (2) objectively follow the response to therapy, and (3) differentiate a cardiac from a pulmonary limitation to exercise.