The ventilatory response to exercise was evaluated in 26 normal sedentary men and 68 patients with chronic heart failure using the slope of the relation between minute ventilation (VE) and carbon dioxide production (VCO2). All subjects underwent maximal upright bicycle cardiopulmonary exercise testing; 33 patients also underwent right-sided cardiac catheterization. The slope of VE/VCO2 was calculated by linear regression analysis using data from all the exercise tests and the first 60% of exercise duration; a high correlation was seen between these results (r = 0.83; p less than 0.001). The slope of VE/VCO2 was significantly, though weakly, related to peak exercise work load, oxygen consumption and ventilatory threshold (r = -0.49, -0.56 and -0.49, respectively), several peak exercise hemodynamic parameters and peak exercise dead space/tidal volume ratio (r = 0.70). With use of multivariate analysis, the only independent determinants of the slope were peak exercise dead space/tidal volume ratio and cardiac index. Thus, in patients with heart failure, exercise hyperventilation can contribute to the impairment of functional capacity and can be considered a compensatory response to abnormal hemodynamics and lung blood distribution in order to keep blood gas concentrations normal.