Exchange-transferred nuclear Overhauser experiments (NOE) probe the three-dimensional conformation of small-molecule ligands bound to macromolecules and have been used to study ligand structural features in a number of ligand-protein complexes. A complete rate matrix analysis, including interactions between the ligand and macromolecule, of a selective saturation, one-dimensional transferred experiment is reported here to supplement previous matrix descriptions for inversion recovery, two-dimensional experiments. Simulation studies allowed a comparison of the magnitude of indirect relaxation effects from pathways involving the protein between these alternative perturbation experiments. The results show that the effect on a ligand-ligand transferred-NOE intensity from protein indirect relaxation pathways varies between a saturation 1D experiment and a recovery 2D experiment. Attenuation by intermolecular indirect relaxation is diminished in the saturation experiment, while intermolecular relaxation effects that increase the direct NOE intensity are somewhat larger in the saturation experiment. These variations between alternative perturbations result from the relatively large NOE magnetization of the protein spins produced by the continuous saturation of a ligand spin and the particular averaging of NMR relaxation rates when the ligand is in molar excess and undergoes fast exchange. The variation observed in the indirect effect from intermolecular pathways in an exchange system does not occur either with intramolecular pathways or in the absence of exchange. The theoretical results suggest that a ratio of NOE intensities from 1D saturation and 2D recovery experiments may be used to indicate regions of close contact between ligand and protein.