Background The contribution of the lung or the plant gain ( PG ; ie, change in blood gases per unit change in ventilation) to Cheyne-Stokes respiration ( CSR ) in heart failure has only been hypothesized by mathematical models, but never been directly evaluated. Methods and Results Twenty patients with systolic heart failure (age, 72.4±6.4 years; left ventricular ejection fraction, 31.5±5.8%), 10 with relevant CSR (24-hour apnea-hypopnea index [ AHI ] ≥10 events/h) and 10 without ( AHI <10 events/h) at 24-hour cardiorespiratory monitoring underwent evaluation of chemoreflex gain (CG) to hypoxia ([Formula: see text]) and hypercapnia ([Formula: see text]) by rebreathing technique, lung-to-finger circulation time, and PG assessment through a visual system. PG test was feasible and reproducible (intraclass correlation coefficient, 0.98; 95% CI , 0.91-0.99); the best-fitting curve to express the PG was a hyperbola ( R≥0.98). Patients with CSR showed increased PG , [Formula: see text] (but not [Formula: see text]), and lung-to-finger circulation time, compared with patients without CSR (all P<0.05). PG was the only predictor of the daytime AHI ( R=0.56, P=0.01) and together with the [Formula: see text] also predicted the nighttime AHI ( R=0.81, P=0.0003) and the 24-hour AHI ( R=0.71, P=0.001). Lung-to-finger circulation time was the only predictor of CSR cycle length ( R=0.82, P=0.00006). Conclusions PG is a powerful contributor of CSR and should be evaluated together with the CG and circulation time to individualize treatments aimed at stabilizing breathing in heart failure.