1. A previous study showed that when combined with exercise in normal subjects, hypercapnic and hypoxic ventilatory stimuli did not have a specific effect on the intensity of the sensation of breathlessness in addition to their stimulation of ventilation. The aim of the present study was to assess the significance of another reflex ventilatory stimulus, metabolic acidosis, in the genesis of this sensation. 2. Six subjects performed progressive exercise tests (mean workload, 103 W; range, 88-125 W) with normal acid-base status. Following NH4Cl-induced metabolic acidosis (mean change in base excess, -3.6 mmol l-1; range, -0.3 to -6.8 mmol l-1) exercise was repeated (mean workload, 91 W; range, 53-116 W) such that the combined ventilatory stimulation resulted in levels of ventilation (mean maximum, 65 l min-1) 'matched' to those resulting from exercise alone. A third, 'matched ventilation', exercise test was performed during metabolic acidosis but with end-tidal PCO2 controlled to a normal level (mean workload, 56 W; range, 17-103 W). Breathlessness was assessed using a visual analogue scale (VAS). 3. Progressive hypercapnic ventilatory stimulation was given before (mean maximum end-tidal PCO2 (PET,CO2), 61 mmHg) and during metabolic acidosis (mean maximum PET,CO2, 57 mmHg) to achieve the same peak level of ventilation (mean maximum, 59 l min-1). Breathlessness was assessed with the VAS. 4. As ventilation increased during a test, there were no statistically significant differences in the increasing breathlessness scores with metabolic acidosis compared to control, for either exercise (mean VAS, 22 mm vs. 24 mm) or progressive hypercapnia (mean peak VAS, 31 mm vs. 32 mm). 5. These results do not support the idea that metabolic acidosis is associated with a change in the relationship between the intensity of breathlessness and ventilation; this is similar to results found with other reflex ventilatory stimuli. 6. These findings are consistent with the hypothesis that the degree of reflex ventilatory activation is an important determinant of the intensity of the sensation of breathlessness in healthy humans, irrespective of the exact nature of ventilatory stimulus.