Brainstem NHE-3 expression in central chemosensitive regions has been shown to correlate inversely with base-line alveolar ventilation (V_A) in conscious rabbits (Wiemann et al., Am. J. Respir. Crit. Care Med. 172, 244–249, 2005). Here the possible influence of chronic respiratory or chronic metabolic acidosis was investigated in two groups of rabbits, either exposed to CO₂-enriched air for 72 h (N=5) or to NH₄Cl with the drinking water for the last two days of a one week period on low-alkali diet (N=6). By means of real-time RT-PCR brain-stem NHE-3 mRNA was quantified (numbers below give fg cDNA /mgRNA). Compared to means ±SEM in untreated controls (NHE-3: 1.42 ±0.29 and V_A: 821 ±42 ml·min^-1, N=13), results during chronic hypercapnia were not significantly different, but NHE-3 was considerably higher (3.57 ±0.39) and V_A was concomitantly de-pressed (to 555 ±52 ml·min^-1) during chronic metabolic acidosis (*P<0.01). In the latter situation, enhanced expression of the sodium/proton exchanger in central chemosensors may be a factor to limit reactive hyperventilation and loss of CO₂, which could help to save bicarbonate buffer during chronic metabolic acidosis.