Two tryptic fragments of the Ca2+ -binding protein calmodulin have been studied by high-resolution 1H NMR. TR1C (residues 1 - 77) spans the first two domains of the protein and TR2C (residues 78 - 148) spans the second two domains. The spectra indicate that each of the two-domain peptides assumes a conformation which is very close to that in the native protein. This characteristic holds both in the presence and in the absence of Ca2+ ions. Therefore, the resonance assignments obtained for the relatively simpler fragment spectra can be used to assign the spectrum of whole calmodulin. Analysis of the chemical shift patterns and nuclear Overhauser enhancement effects of several assigned resonances indicates that each half of calmodulin can be modelled after the two EF-hand Ca2+-binding proteins for which crystal structures are available, namely parvalbumin and intestinal Ca2+-binding protein.