The first bicarbonate pool sizes and kinetic data necessary for the interpretation of substrate oxidation studies have been determined in six fed, nonacidotic infants, ages 2.5 to 5 months. Following an intravenous bolus of NaH13CO3 (50 mumol/kg), breath samples were collected over 240 min for the analysis of breath 13CO2. Each breath 13CO2 disappearance curve was fitted to a multicompartmental bicarbonate model previously derived in adults. The mean sizes of the three bicarbonate pools were: 7.4 +/- 0.8 mmol/kg (central pool), 15.1 +/- 4.8 mmol/kg (rapidly exchanging peripheral pool), and 8.8 +/- 3.5 mmol/kg (slowly exchanging peripheral pool). The mean percentage dose recovery was 57 +/- 10%. The pool sizes suggested that extensive metabolic exchange of carbon between HCO3- and organic metabolites occurred in the infant.