Reactions of diol epoxide metabolites of carcinogenic poly cyclic aromatic hydrocarbons with DNA are thought to initiate the carcinogenic process1,2. Although formation of a benzo[a]pyrene (BaP) diol epoxide-deoxyguanosine adduct has been held responsible for biological activity3–5, the more potent carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA) binds extensively to deoxyadenosine residues in DNA, suggesting that hydrocarbon carcinogen-deoxyadenosine adducts may be instrumental in tumour initiation6–8. Because the bay region diol epoxides9 of benzo[c]phenanthrene (BcPh) are very active tumour initiators10, and the relative activities of the four configurationally isomeric 3,4-diol 1,2-e pox ides (Fig. 1) are known11, we examined their reactions with DNA. Each BcPh diol epoxide isomer exhibits a remarkable preference for covalent binding to DNA over hydrolysis, each yields a unique distribution of products with the nucleosides of DNA and each reacts extensively with deoxyadenosine residues in DNA. The relative tumour initiating activities of these stereoisomers is best reflected by the relative yields of one of the deoxyadenosine adducts formed.