Carbon dioxide entry rates (CER) based on isotopic activities in either expired air or blood following a 24-h intravenous infusion of [13C]- and [14C] sodium bicarbonate were compared with CO2 production quantified by respiration hood in young sheep (28-30 kg) either fed (three animals) or fasted (three animals). CO2 production increased with intake (5.2 vs 10.3 mol/day; P < 0.001) as did CER values based on expired air (9.9 vs 18.6 mol/day; P < 0.001) or blood (7.5 vs 16.5 mol/day; P < 0.001). The differences between air and blood CER values were significant (P < 0.001). There were no differences, however, when data were compared between [13C] and [14C] measurements. How much of these differences could be attributed to sequestration of label in body tissues was examined at the end of the infusion. The highest specific radioactivities (dpm/g dry matter) in acid-fast tissue material were observed for the more metabolically active tissues, liver, jejunum and kidney, with the lowest values for fat and muscle. When tissue mass was taken into account, however, the largest proportions of the dose sequestered were in bone muscle, skin and fat with significantly more retained for the former three (P < 0.01) during fasting. Separately, losses as urinary urea were also quantified. Total measured sequestration of label only accounted for approximately 24-44% of the difference between CER and CO2 production.