TCDD is the most toxic member of a class of polyhalogenated aromatic hydrocarbons that are structurally related, have a similar mechanism of action, and cause the same spectrum of responses. Because of the need to assess the risk from complex mixtures of these chemicals, the international community has adopted an interim approach that assigns relative potency factors to this family of chemicals, based on a comparison with the potency of TCDD. Each chemical that fits the criteria for this class is assigned a toxic equivalency factor, TEF, which is some fraction of that of TCDD. The total toxic equivalency of a mixture, TEQ, is the sum of the weighted potency of each compound in the mixture. Although there may be some variability between different responses in the determination of a TEF value for a compound, endpoint-specific TEFs are usually very similar. There may also be some species differences in TEFs. Again, if pharmacokinetic factors are taken into account, they are usually relatively minor. TEFs based on intake values may also exhibit some differences when compared to those based on target tissue concentrations. Using scientific judgment and a broad data base, interim TEF values have been recommended for PCDDs, PCDFs, and dioxin-like PCBs. Using such values, the TEF approach has been successful at predicting the toxicity of real world mixtures. Ongoing studies from our laboratory have validated the approach for synthetic mixtures that approximate congener ratios found in food samples. Whether non-additive interactions occur with nondioxin-like compounds found in environmentally relevant concentrations remain to be determined.