DNA strand scission by the bleomycin analogs talisomycin S10b and a novel fluorescent mimic, fluoromycin, has been characterized and compared with that of bleomycin A2. Both analogs were found to have essentially the same sequence specificity for DNA strand scission as bleomycin A2. As observed with bleomycin A2, the preferred sites of DNA cleavage by talisomycin S10b and fluoromycin were 5'-GpT-3' and 5'-GpC-3'. These results suggest that the DNA sequence selectivity of bleomycins remains unaltered upon modification of the C-terminal domain.