The metabolic contributions to chronic acid-base changes were examined in the plasma of arterial blood in patients with chronic obstructive pulmonary disease (COPD) and chronic hypercapnia, by a quantitative physical-chemical analysis. Patients were stratified into three groups: group 1 (Paco2 less than 40 mmHg; 1 mmHg = 133.3 Pa), group 2 (Paco2 between 40 and 50 mmHg), and group 3 (Paco2 higher than 50 mmHg). With the development of hypercapnia (Paco2 from 38.2 +/- 1.6 to 53.8 +/- 0.6 mmHg) and hypoxemia (Pao2 from 73.6 +/- 2.5 to 62.1 +/- 2.1 mmHg), blood pH decreased slightly (from 7.405 +/- 0.007 to 7.372 +/- 0.009). The strong ion difference ([SID]) increased in the hypercapnic group (from 39.7 +/- 1.7 to 46.2 +/- 2.9 mequiv.L-1) parallel to the increase in [HCO3-] (from 23.8 +/- 0.5 to 30.8 +/- 0.8 mequiv.L-1). The change in [SID] was quantitatively similar to the [HCO3-] change, thus reflecting a metabolic compensation of chronic respiratory acidosis. [SID] increase was mainly accounted for by changes in the [Na+]/[Cl-] ratio due to a significant decrease in plasma [Cl-]. Other ions measured as well as the weak acid buffers ([ATOT]) remained constant. From the present results, we suggest the usefulness of the physical chemical approach in the characterization of acid-base disturbances due to chronic hypercapnia when water retention or protein depletion are expected further to hypochloremia, as can be the case in severe COPD patients.