BACKGROUND Halon 1301 and Halon 1211 are being replaced because they contribute to the depletion of ozone. Many of the potential candidate chemicals for replacing them are, like them, halogenated hydrocarbons. These chemicals have the potential to cause cardiac sensitization at high enough exposure concentrations. METHODS A physiologically based pharmacokinetic model, which mathematically describes the uptake, distribution, metabolism, and elimination of chemicals, was used to relate exposure to these chemicals with arterial blood concentrations resulting from the exposure. This information was then used to evaluate the potential for the occurrence of a cardiac-sensitizing event. The model was used to analyze the exposures to Halon 1301 and Halon 1211 in three aircraft (Navy E-2B, Cessna-421B, and Cessna-210C). RESULTS Halon 1301 exposures were shown to be safe, but Halon 1211 resulted in arterial concentrations in exposed individuals that reached levels that could potentially cause cardiac sensitization. CONCLUSIONS Use of the model for evaluating the risk from exposure to Halon 1301 and Halon 1211 is a moot point since both chemicals are being replaced. However, demonstration of the validity of the approach provides a tool for the evaluation of the health safety of replacement candidates. The National Fire Protection Association has approved use of this model for assessing times for safe egress from situations where agents are used to flood an area to extinguish a fire.