This paper reports a novel NMR method for mapping the surface of interaction between proteins and nucleic acids. The method builds upon the cross-saturation based approach recently introduced by Takahashi et al. (Nature Struct. Biol. 2000, 7, 220-223) and takes advantage of the presence of spectral regions which contain nucleic acid signals, but which are devoid of protein resonances, to obviate the requirement for deuteration. The data obtained are complementary to those taken from the widely used chemical shift perturbation method, and a joint analysis of the results of both methods increases the reliability with which the interface can be characterised. The approach has been assessed using a protein-RNA complex for which NMR chemical shift pertubation and X-ray crystallographic data are available.