It has been suggested that hyperventilation and the disproportionate increase in V˙CO2versus V˙O2above the ventilatory threshold (V TH ) in ramp exercise are due to the production of nonmetabolic CO 2 in muscle because of lactic acid buffering by plasma bicarbonate entering the cell in exchange with lactate [Wasserman, K., 1982. Dyspnea on exertion. Is it the heart or the lungs? JAMA 248, 2039–2043]. According to this model, plasma standard bicarbonate concentration decreases in a ∼1:1 ratio with the increase in plasma lactate concentration, 1mmol of CO 2 is generated above that produced by aerobic metabolism for each mmol of lactic acid buffered, and nonmetabolic CO 2 produced in the muscle is partly responsible for hyperventilation because of the resulting increase in the CO 2 flow to the lungs. The present report shows that this model is not consistent with experimental data: (1) bicarbonate is not the main buffer in the muscle; (2) the decrease in standard bicarbonate concentration is not the mirror image of the increase in lactate concentration; (3) buffering by bicarbonate does not increase CO 2 production in muscle (no nonmetabolic CO 2 is produced in tissues); (4) the CO 2 flow to the lungs, which should not be confused with V˙CO2 at the mouth, does not increase at a faster rate above than below V TH . The disproportionate increase in V˙CO2 at the mouth above V TH is due to hyperventilation (not the reverse) and to the low plasma pH which both reduce the pool of bicarbonate readily available in the body.