1. Development of the chemistry of polycyclic aromatic hydrocarbon (PAH) radical cations has provided evidence that these intermediates play a major role in the metabolism of PAHs by P450 and in their binding to DNA. 2. Fluoro substitution of benzo[a]pyrene (BP) represents a suitable probe for studying mechanisms of oxygen transfer in the P450-catalysed formation of quinones and phenols from BP. Formation of BP-1,6-, -3,6- and -6,12-dione from the metabolism of 6-fluoroBP (6-FBP) is mediated by the intermediate 6-FBP+. Similarly, metabolism of 1-FBP and 3-FBP by rat liver microsomes produces BP-1,6-dione and BP-3,6-dione respectively. These results demonstrate that formation of quinones and phenols occurs via an initial electron transfer from BP to P450 and subsequent transfer of oxygen from the iron-oxo complex of P450 to BP. 3. Radical cations also play a major role in the formation of DNA adducts by the potent carcinogens 7,12-dimethylbenz[a]anthracene (DMBA), BP and dibenzo[a,l]pyrene (DB[a,l]P). In the binding of BP both in vitro and in vivo, 80% of the adducts are formed by one-electron oxidation, namely, 8-(BP-6-yl)guanine (BP-6-C8Gua), BP-6-N7Gua and BP-6-N7adenine (Ade), and are lost from the DNA by depurination. For DB[a,l]P, depurinating adducts formed from the radical cation, DB[a,l]P-10-C8Gua, DB[a,l]P-10-N7Gua, DB[a,l]P-10-N7Ade, and DB[a,l]P-10-N3Ade comprise 50% of the total DNA adducts. For DMBA, 99% of the adducts are depurinating adducts formed from the radical cation, 7-CH3BA-12-CH2-N7Gua and 7-CH3BA-12-CH2-N7Ade. 4. In summary, radical cations of PAHs play a major role in both the metabolism and metabolic activation leading to formation of DNA adducts that are critical in the mechanism of tumour initiation.