The intestinal fatty acid binding protein (IFABP) is a small (15 kDa) protein consisting mostly of 10 antiparallel β-strands (A-J) and a small helical region that serves as a portal for the ligand. Two β-sheet structures (strands A-E and F-J) surround a cavity into which the ligand binds. In this work, we investigated how changes in the side chains of specific residues are propagated through the structure. To determine what these changes were and how they relate to changes in stability, 15N chemical shift perturbations were measured and compared to those of the wild-type protein. Seven mutations, five of which change either valine or leucine to glycine, have been examined. All these mutants were less stable than wild-type IFABP, suggesting some structural changes. For five of the mutants, the data suggest that destabilization of a small region of the protein propagates throughout the structure, resulting in an overall decrease in stability. In two (Leu38Gly and Leu89Gly), the loss of cooperativity in the equilibrium denaturation curves suggests that the destabilization of one region may not be transmitted to other regions in a cooperative manner. It is shown that the effect of mutating hydrophobic residues is much greater than that observed upon mutation of a solvent-exposed polar residue.