BACKGROUND: Some environmental chemical exposures are lipophilic and need to be adjusted by serum lipid levels before data analyses. There are currently various strategies that attempt to account for this problem, but all have their drawbacks. To address such concerns, we propose a new method that uses Box-Cox transformations and a simple Bayesian hierarchical model to adjust for lipophilic chemical exposures. METHODS: We compared our Box-Cox method to existing methods. We ran simulation studies in which increasing levels of lipid-adjusted chemical exposure did and did not increase the odds of having a disease, and we looked at both single-exposure and multiple-exposure cases. We also analyzed an epidemiology dataset that examined the effects of various chemical exposure on the risk of birth defects. RESULTS: Compared with existing methods, our Box-Cox method produced unbiased estimates, good coverage, similar power, and lower type I error rates. This was the case in both single- and multiple-exposure simulation studies. Results from analysis of the birth-defect data differed from results using existing methods. CONCLUSION: Our Box-Cox method is a novel and intuitive way to account for the lipophilic nature of certain chemical exposures. It addresses some of the problems with existing methods, is easily extendable to multiple exposures, and can be used in any analysis that involves concomitant variables. Copyright © 2013 by Lippincott Williams & Wilkins.