This investigation elucidated the underlying mechanisms of functional impairments in patients with heart failure (HF) by simultaneously comparing cardiaccerebral- muscle hemodynamic and ventilatory responses to exercise among HF patients with various functional capacities. One hundred one patients with HF [New York Heart Association HF functional class II (HF-II, n = 53) and functional class III (HF-III, n = 48) patients] and 71 normal subjects [older control (O-C, n = 39) and younger control (Y-C, n = 32) adults] performed an incremental exercise test using a bicycle ergometer. A recently developed noninvasive bioreactance device was adopted to measure cardiac hemodynamics, and near-infrared spectroscopy was employed to assess perfusions in the frontal cerebral lobe ($Δ$[THb] FC) and vastus lateralis muscle ($Δ$ [THb] VL). The results demonstrated that the Y-C group had higher levels of cardiac output, $Δ$ [THb] FC, and $Δ$ [THb] VL during exercise than the O-C group. Moreover, these cardiac/peripheral hemodynamic responses to exercise in HF-III group were smaller than those in both HF-II and O-C groups. Although the change of cardiac output caused by exercise was normalized, the amounts of blood distributed to frontal cerebral lobe and vastus lateralis muscle in the HF-III group significantly declined during exercise. The HF-III patients had lower oxygen-uptake efficiency slopes (OUES) and greater V E-VO 2 slopes than the HF-II patients and age-matched controls. However, neither hemodynamic nor ventilatory response to exercise differed significantly between the HF-II and O-C groups. Cardiac output, $Δ$ [THb] FC, and $Δ$ [THb] VL during exercise were directly related to the OUES and VO 2peak and inversely related to the V E-VCO 2 slope. Moreover, cardiac output or $Δ$ [THb] FC was an effect modifier, which modulated the correlation status between $Δ$ [THb]VL and V E-VCO 2 slope. We concluded that the suppression of cerebral/muscle hemodynamics during exercise is associated with ventilatory abnormality, which reduces functional capacity in patients with HF. © 2011 the American Physiological Society.