The extracellular pH defense against the lactic acidosis resulting from exercise can be estimated from the ratios -delta[La].delta pH-1 (where delta[La] is change in lactic acid concentration and delta pH is change in pH) and delta[HCO3-].delta pH-1 (where delta[HCO3-] is change in bicarbonate concentration) in blood plasma. The difference between -delta[La].delta pH-1 and delta[HCO3-].delta pH-1 yields the capacity of available non-bicarbonate buffers (mainly hemoglobin). In turn, delta[HCO3-].delta pH-1 can be separated into a pure bicarbonate buffering (as calculated at constant carbon dioxide tension) and a hyperventilation effect. These quantities were measured in 12 mountaineers during incremental exercise tests before, and 7-8 days (group 1) or 11-12 days (group 2) after their return from a Himalayan expedition (2800-7600 m altitude) under conditions of normoxia and acute hypoxia. In normoxia -delta[La].delta pH-1 amounted to [mean (SEM)] 92 (6) mmol.l-1 before altitude, of which 19 (4), 48 (1) and 25 (3) mmol.l-1 were due to hyperventilation, bicarbonate and non-bicarbonate buffering, respectively. After altitude -delta[La].delta pH-1 was increased to 128 (12) mmol.l-1 (P < 0.01) in group 1 and decreased to 72 (5) mmol.l-1 in group 2 (P < 0.05), resulting mainly from apparent large changes of non-bicarbonate buffer capacity, which amounted to 49 (14) mmol.l-1 in group 1 and to 10 (2) mmol.l-1 in group 2. In acute hypoxia the apparent increase in non-bicarbonate buffers of group 1 was even larger [140 (18) mmol.l-1]. Since the hemoglobin mass was only modestly elevated after descent, other factors must play a role. It is proposed here that the transport of La- and H+ across cell membranes is differently influenced by high-altitude acclimatization.