We measured uptake of halothane (the fraction of halothane in expired gas divided by the fraction of halothane in inspired gas, FE/FI) with a mass spectrometer over time in 7 infants less than 3 months of age. FE/FI for halothane in these infants increased more rapidly than has been described in adults by others. In addition, we developed a mathematical model for halothane uptake and distribution that incorporates age-dependent anatomic and physiologic parameters (alveolar ventilation, functional residual capacity, cardiac output, brain volume, etc). The model closely predicts FE/FI for halothane measured in the infants. At 5 min observed FE/FI was 0.67, at 15 min observed FE/FI was 0.80, while the predicted FE/FI values were 0.65 and 0.82, respectively. The model predicts that the myocardial and brain halothane concentrations will increase more rapidly in the infant than in the adult. Achievement of high myocardial halothane concentrations early in the anesthetic induction may cause the hypotension and bradycardia commonly seen in infants. Sensitivity of the infant myocardium to halothane would further exacerbate the effect of more rapid myocardial uptake.