The present study evaluates the sensitivity of pharmacokinetic model output to variability in the biochemical and metabolic input parameters. Pharmacokinetic models of three chemicals are chosen for analysis: styrene, methylchloroform, and methylene chloride. Results show that model sensitivities are time-, dose-, and species-dependent and that the most sensitive parameters are the maximum Michaelis-Menten metabolism rate Vmax and the blood/air and fat/air partition coefficients. For humans, the muscle/air partition coefficient is also important. Model output is insensitive to the Michaelis-Menten parameter Km (except for low doses) and to other tissue/air partition coefficients.