Adenine, guanine, and native and denatured DNA lower the overpotential for the reduction of Ni(II) at a mercury electrode in a sodium acetate medium. A mechanism for the electrode reaction underlying the electrocatalytic effects observed is proposed. The similarity of the electrocatalytic effects of native and thermally denatured DNA adsorbed on the electrode at full coverage reveals that Ni(II) species interact with basic residues within the double-helical structure, thus reflecting the high diffusivity of these species throughout the native DNA molecule. A simple differential pulse voltammetric method for the simultaneous determination of adenine and guanine in mixtures based on the peak for the reduction of protonated adenine and the single prepeak produced by the reduction of Ni(II) catalysed by unprotonated adenine and guanine was developed. Finally, a sensitive adsorptive stripping differential pulse voltammetric method for the determination of native and denatured DNA is proposed.