The interaction of calf thymus DNA with Cu2+ and Pb2+ was studied in aqueous solution at pH 6.5 with metal/DNA (P) (P = phosphate) molar ratios (r) 1/80, 1/40, 1/20, 1/10, 1/4, 1/2, and 1, using Fourier Transform ir (FTIR) spectroscopy. Correlations between the ir spectral changes, metal ion binding mode, DNA condensation, and denaturation, as well as conformational features, were established. Spectroscopic evidence has shown that at low metal/DNA (P) molar ratios 1/80 and 1/40, copper and lead ions bind mainly to the PO2- of the backbone, resulting in increased base-stacking interaction and duplex stability. The major copper ion base binding via G-C base pairs begins at r > 1/40, while the lead ion base binding occurs at r > 1/20 with the A-T base pairs. The denaturation of DNA begins at r = 1/10 and continues up to r = 1/2 in the presence of copper ions, whereas a partial destabilization of the helical structure was observed for the lead ion at high metal ion concentration (r = 1/2). Metal-DNA binding also results in DNA condensation. No major departure from the B-family structure was observed, upon DNA interaction with these metal ions.