Proteins recognize ligands by forming specific intermolecular interactions that often involve solvent exposed residues. Changes in the motional properties of these residues upon binding can affect the conformational entropy of the system and thus are related to the energetics of binding. The role that dynamics plays in ligand recognition can be investigated by comparing the motional properties of a free and ligated protein. NMR relaxation studies are well suited for examining changes in dynamics, especially for motions on a nanosecond to picosecond time scale. Recently, we determined the solution structure of the phosphotyrosine binding (PTB) domain of the insulin receptor substrate (IRS-1) complexed to a tyrosine-phosphorylated peptide derived from the interleukin 4 (IL-4) receptor [Zhou et al., (1996) Nat. Struct. Biol. 3, 388-393]. The peptide binds tightly to the protein in a surface exposed pocket, resulting in the partial burial of many protein residues. Using NMR relaxation studies, the dynamics of the backbone nitrogens of IRS-1 PTB domain were studied in both the free protein and the protein when complexed to the IL-4 receptor phosphopeptide. The backbone nitrogens of many residues that make important contacts to the ligand are motionally restricted in the free and complexed protein. Additional residues become motionally restricted only after ligand binding, including several residues that do not make any direct contacts with the ligand. These observed changes in the dynamics are compared to structural features of the complex.