A contrathermodynamic sequence selectivity (5'-deoxyadenosine > 5'-deoxyguanosine) for UV-irradiation-induced strand damage in duplex DNA containing 5-bromo-2'-deoxyuridine was reported several years ago (Saito, I.; Sugiyama, H. J. Ant. Chem. Sec. 1990, 112, 6720.). In contrast, much smaller sequence selectivity was observed for similar duplexes containing 5-iodo-2'-deoxyuridine. We investigated the mechanism of UV-irradiation-induced cleavage of duplex DNA containing 5-bromo-2'-deoxyuridine (1, BrdU) and 5-iodo-2'-deoxyuridine (2, IdU) under anaerobic conditions using a variety of structural probes. The preference for UV-induced cleavage in 5'-dABrdU sequences is a confluence of at least three factors, photoinduced forward electron transfer, charge recombination, and electron migration within the DNA duplex. Our results also indicate that UV-irradiation of duplexes (32 nucleotides long) containing 5-iodo-2'-deoxyuridine results in strand scission involving initial photoinduced single electron transfer. The selectivity for 5'-dAIdU sequences is smaller than that in the analogous 5-bromo-2'-deoxyuridine duple res and may be the result of fas ter dehalogenation of the initially formed 5-halopyrimidine radical anion and/or competitive direct carbon-iodine bond homolysis.