Patients with chronic heart failure have an abnormal pattern of exercise ventilation (V_E), characterized by small tidal volumes (V_T), increased alveolar ventilation, and elevated physiologic dead space (V_D/V_T). To investigate whether increased lung water in isolation could reproduce this pattern of exercise ventilation, 30 ml/kg of saline was rapidly infused into nine normal subjects, immediately before a symptom-limited incremental exercise test. Saline infusion significantly reduced forced vital capacity, 1-s forced expiratory volume and alveolar volume (p <0.01 for all). After saline, exercise ventilation assessed by the V_E /V_CO2 slope increased from 24.9 ± 2.4 to 28.0 ± 2.9 L/L, (p<0.0002), associated with a small decrease in PaCO₂, but without changes in V_T, V_D/V_T or alveolar-arterial O₂ difference ((A-a)DO₂). A reduction in maximal oxygen uptake (VO_2max) of 175 ± 184 ml/min (p<0.02) was observed in the post-saline infusion exercise studies, associated with a consistent reduction in maximal exercise heart rate (8.1 ± 5.9 beat/min p<0.01), but without a change in the O₂ pulse. Therefore, infusion of saline to normal subjects prior to exercise failed to reproduce either the increase in V_D/V_T or the smaller exercise V_T described in heart failure patients. The observed increase in V_E can be attributed to dilution acidosis from infusion of the bicarbonate-free fluid and/or to afferent signals from lung and exercising muscles. The reduction in maximal power output, VO_2max, and heart rate after saline infusion may be linked to accumulation of edema fluid in exercising muscle, impairing the diffusion of oxygen to muscle mitochondria.