A sequential procedure, based on 2D NOE spectroscopy, is described for identifying the resonances of water-exchangeable imino protons in NMR spectra of oligonucleotides. The adenine H2 and amino protons are also part of the cross-relaxation network of the imino protons and their resonance frequencies are easily found in the 2D NOE spectra. The NOE contacts between the amino and H5 protons of cytidines form an independent check for the correctness of the assignments, since these CHS protons are also part of the cross-relaxation network formed by the nonexchangeable protons, for which another sequential-assignment procedure exists (R. M. Scheek et al., J. Am. Chem. Soc.14, 2914 (1983)). The method was applied to a 14 bp lac operator fragment. The assignments of the resonances of the water-exchangeable imino and amino protons in this DNA fragment are required for studying its complex with the lac repressor headpiece.