Previous studies from this laboratory have characterized the "whole-body" response to acute hypercapnia in normal dog and humans. A more recent investigation has demonstrated that this response is markedly altered by graded degrees of chronic respiratory acidosis. The present studies were carried out to assess the influence, if any, of chronic metabolic acid-base disturbances on the acute CO2 titration curve in the dog. To this purpose we first produced a broad range of chronic plasma bicarbonate concentration of metabolic nature. Metabolic acidosis (n = 14) was produced by prolonged HCl-feeding and metabolic alkalosis (n = 11) by diuretics and a chloride-free diet. Animals with normal acid-base status (n = 4) were also studied. After the establishment of a chronic steady state of acid-base equilibrium, we then performed an acute CO2 titration of the unanesthetized dogs within a large environmental chamber. Three levels of inspired CO2 fraction (FICO2) were employed ranging from 4 to 15%. The results indicate that chronic metabolic acid-base disturbances exert a dramatic influence on the whole-body response to acute hypercapnia. The acute change in plasma bicarbonate for a given change in partial pressure of CO2 in arterial blood (PaCO2) or plasma pH decreases as a function of the chronic level of plasma bicarbonate concentration. Yet the ability of the organism to defend plasma hydrogen ion concentration is progressively strengthened as the chronic level of plasma bicarbonate increases.(ABSTRACT TRUNCATED AT 250 WORDS)