A number of approaches have been employed to elucidate the causes of organ and species specificity. In the earlier studies, homogenates of various tissues were used to metabolically activate the chemical; however, metabolite profiles, DNA-adduct profiles, and induced mutagenic responses of cell homogenates differ from those of intact cells. More recent studies have looked at the nature of carcinogen metabolites and DNA-adducts formed in cells or tissues or at the nature and persistence of DNA-adducts in in vivo tissues. Differences in the results from these various approaches are apparent. In addition, the nature and amount of DNA-adducts are only correlated with the biological response expected in the tissue. The ability to measure a biological response from system well as parameters such as chemical metabolism, DNA adducts, DNA repair, etc., would provide a useful system for elucidating some of the biological mechanisms leading to the phenomena of specificity.