This study investigated the effect of high CO2 (4%) from embryonic day (ED) 10 until ED16 on the acid-base balance and related parameters in the chicken embryo. From ED10 to ED16, blood was taken from a vein from the chorioallantois membrane and was analyzed for pH, partial pressure of CO2, partial pressure of O-2 (pO(2)), [HCO3-], [K+], and [Ca2+]. Allantoic fluid was taken for measurement of pH, NH3-N, phosphate, and calcium concentration. The right tibia was ashed, and calcium was measured with atomic absorption spectroscopy. Embryos exposed to high CO2 showed a consistent higher blood pH than control embryos. Notwithstanding this alkalosis, bicarbonate concentration was significantly higher in the CO2 group from ED12 until ED16. Potassium concentration in the blood was significantly higher in the CO2 group from ED11 until ED16. The pH of the allantois was significantly higher on ED14 and ED15. Ammonia N concentration was significantly higher in the CO2-incubated embryos on ED12 and ED13, whereas phosphate did not differ between groups. Calcium per tibia dry weight did not differ between incubation conditions. We can conclude that embryos adapt to high CO2 during the second half of incubation by increasing blood HCO3(-). It appears that this increase in HCO3- is mainly the result of the stimulated intracellular exchange of H+ with K+, although temporary reabsorption of HCO3- by the kidney cannot be excluded.