Extracellular acidosis has been demonstrated to play a key role in the process of metabolic depression under long-term environmental stress, exemplified in the marine invertebrate Sipunculus nudus. These findings led to the hypothesis that acid-base regulation is associated with a visible cost depending on the rate and mode of H+-equivalent ion exchange. To test this hypothesis, the effects of different ion-transport inhibitors on the rate of pH recovery during hypercapnia, on energy turnover and on steady-state acid-base variables were studied in isolated body wall musculature of the marine worm Sipunculus nudus under control conditions (pHe 7.90) and during steady-state extracellular acidosis (pHe 7.50 or 7.20) by in vivo 31P-NMR and oxygen consumption analyses. During acute hypercapnia (2 % CO2), recovery of pHi was delayed at pHe 7.5 compared with pHe 7.9. Inhibition of the Na+/H+-exchanger by 5-(N,N-dimethyl)-amiloride (DMA) at pHe 7.5 delayed recovery even further. This effect was much smaller at pHe 7.9. Inhibition of anion exchange by the addition of the transport inhibitor 4,4Ž-diisothiocyanatostilbene-2,2Ž-disulphonic acid (DIDS) prevented pH recovery at pHe 7.5 and delayed recovery at pHe 7.9, in accordance with an effect on Na+-dependent Cl-/HCO3- exchange. The effects of ouabain, DIDS and DMA on metabolic rate were reduced at low pHe, thereby supporting the conclusion that acidosis caused the ATP demand of Na+/K+-ATPase to fall. This reduction occurred via an inhibiting effect on both Na+/H+- and Na+-dependent Cl-/HCO3- (i.e. Na+/H+/Cl-/HCO3-) exchange in accordance with a reduction in the ATP demand for acid-base regulation during metabolic depression. Considering the ATP stoichiometries of the two exchangers, metabolic depression may be supported by the predominant use of Na+/H+/Cl-/HCO3- exchange under conditions of extracellular acidosis.