Two strategies for assessment of the toxicity of complex mixtures are described and illustrated with examples from genotoxicity studies of complex combustion mixtures. The first is a strategy for identifying biologically active compounds or compound classes in complex mixtures (bioassay-directed fractionation and characterization). Studies have shown that a significant portion of the mutagenicity in combustion emissions and urban air is found in fractions more polar than polynuclear aromatic hydrocarbons. The second strategy (comparative potency method) provides an approach to evaluating the relative toxicities of a series of mixtures. The comparative mutagenicity and carcinogenicity of a series of combustion emissions has been assessed using dose-response studies in bacteria, mammalian cells, and rodents. Comparative mutagenic and tumorigenic emission rates or emission factors provide a means to directly compare the relative hazard of the sources. The data base also has been used to develop a comparative risk assessment methodology for combustion emissions.