Intense exercise causes fatigue development and ultimately exhaustion within few minutes but the exact mechanisms protecting the myocyte from detrimental ATP depletion remains controversial. Here, the hypothesis that a reduced extracellular pH and HCO3- level would accelerate intramuscular metabolic acidosis and impair exercise performance was evaluated. Seven healthy males (25±4 yrs; mean ±SD) participated in the double-blind placebo controlled experiment where intermittent isometric exercise was performed as 2 s contraction at 60±6 % of maximal voluntary contraction force (MVC) followed by 1 s rest until exhaustion. Each of three situations (oral intake of: 0.5 g × kg b.w.-1 NaHCO3; 0.3 g × kg b.w.-1 NH4Cl; 0.3 g × kg b.w.-1 CaCO3) was studied on two occasions. On one occasion intramuscular pH was monitored continuously using 31P-NMR and on the other muscle function was continuously monitored by conduction of MVC’s and induction of a twitch contraction by single pulse electrical stimulation every 30th second until exhaustion. Prior to exercise capillary blood pH was higher (P<0.001) in NaHCO3 (7.48±0.02) than CaCO3 (7.41±0.01) which was higher (P<0.05) than in NH4Cl (7.30±0.07). Likewise, blood HCO3- was higher (P<0.001) in NaHCO3 (32.5±3.4 mM) than CaCO3 (24.5±1.8 mM) which was higher (P<0.05) than in NH4Cl (18.9±4.6 mM). Time to exhaustion (TTE) was similar between trials. In the NMR experiment TTE was 6.3±1.4 min; 6.2±0.8 min, 6.1±1.3 min in NaHCO3, CaCO3, NH4Cl, respectively. In the muscle function experiment TTE was 4.0±2.2; 4.8±1.9; 5.5±4.5 min in NaHCO3, CaCO3, NH4Cl, respectively. Likewise, the reduction of intramuscular pH was similar between trials (Fig. 1) and so was the reduction in MVC (Fig. 2) and electrically induced twitch force (Data not shown). This is the first study in which acid/base homeostasis is manipulated by intake of NaHCO3 and NH4Cl in vivo in combination with a high temporal resolution analysis of intramuscular metabolic acidosis as well as muscle function. The present findings demonstrate that manipulation of extracellular acid and base homeostasis has no effect on deterioration of m. tibialis anterior muscle function during exhaustive intermittent static exercise. Further, the findings indicate that myocyte outward H+ flux in conditions of metabolic stress cannot be accelerated by an increased H+ gradient and elevated extracellular buffer capacity. In a practical context, the finding questions the use of NaHCO3 as a performance enhancing agent, at least in sports engaging only a limited muscle mass.