Petroleum hydrocarbon mixtures such as gasoline, diesel fuel, aviation fuel, and asphalt liquids typically contain hundreds of compounds. These compounds include aliphatic and aromatic hydrocarbons within a specific molecular weight range and sometimes lesser amounts of additives, and often exhibit qualitatively similar pharmacokinetic (PK) and pharmacodynamic properties. However, there are some components that exhibit specific biological effects, such as methyl t-butyl ether and benzene in gasoline. One of the potential pharmacokinetic interactions of many components in such mixtures is inhibition of the metabolism of other components. Due to the complexity of the mixtures, a quantitative description of the pharmacokinetics of each component, particularly in the context of differing blends of these mixtures, has not been available. We describe here a physiologically-based pharmacokinetic (PBPK) modeling approach to describe the PKs of whole gasoline. The approach simplifies the problem by isolating specific components for which a description is desired and treating the remaining components as a single lumped chemical. In this manner, the effect of the non-isolated components (i.e. inhibition) can be taken into account. The gasoline model was based on PK data for the single chemicals, for simple mixtures of the isolated chemicals, and for the isolated and lumped chemicals during gas uptake PK experiments in rats exposed to whole gasoline. While some sacrifice in model accuracy must be made when a chemical lumping approach is used, our lumped PK model still permitted a good representation of the PKs of five isolated chemicals (n-hexane, benzene, toluene, ethylbenzene, and o-xylene) during exposure to various levels of two different blends of gasoline. The approach may be applicable to other hydrocarbon mixtures when appropriate PK data are available for model development.