(CO)-C-59 NMR and CD measurements show for both stereoisomers of Co(en)(3)(3+) a similar trend in the sequence dependence of DNA recognition, as was reported previously for Co(NH3)(6)(3+). In particular, specific binding is evident to DNA molecules possessing runs of two or more same-strand guanine residues. The binding of either isomer to such sequences induces structural transitions toward A-DNA characteristics. Such measurements also show significant differences between the two stereoisomers in terms of how they recognize specific duplex DNA sequences. Delta-Co(en)(3)(3+) binds more tightly than Lambda-Co(en)(3)(3+) to right-handed, guanine-rich DNA, whereas Lambda-Co(en)(3)(3+) binds more tightly than Delta-Co(en)(3)(3+) to left-handed DNA. The two stereoisomers bind in an indistinguishable manner to AT-rich DNA.