The redistribution of CO2 and bicarbonate throughout the body following perturbations of normal respiration is not well described. We used tracer techniques to examine CO2-bicarbonate dynamics in an animal model in which acute hypercapnia was induced by hypoventilation. Eleven rabbits were anesthetized, tracheostomized, paralyzed and ventilated. In five animals PaCO2 was kept between 30 and 35 mmHg (control, C) while in six PaCO2 was held between 65 and 70 mmHg (acute hypercapnia, AH). A bolus of [13C]bicarbonate was given intravenously. Breath samples were obtained for 13CO2 by isotope ratio mass spectrometry and CO2 output (VCO2) was measured breath-by-breath for 240 min. There was no difference in the VCO2 between C [5.6 +/- 1.8 (SD) ml/min per kg] and AH (5.3 +/- 0.8). The 13CO2 washout for both C and AH was well fit by the sum of three exponentials. Only the time constant of the third (slowest) exponential was significantly longer in AH (103 +/- 11 min) compared with C (75 +/- 15, P less than 0.01). The mean residence time in AH (82 +/- 9 min) was significantly lower than in C (57 +/- 10, P less than 0.001). The estimated mass of exchangeable CO2 and bicarbonate was significantly greater in AH (443 +/- 37 ml per kg) compared with C (312 +/- 63, P less than 0.005). Compartmental analysis indicated that the increase in CO2-bicarbonate occurred primarily in the slowly exchanging pool. The data suggest that acute hypercapnia may be accompanied by a redistribution of exchangeable CO2 and bicarbonate in the body.