Determination of the 3D structures of multidomain proteins by solution NMR methods presents a number of unique challenges related to their larger molecular size and the usual scarcity of constraints at the interdomain interface, often resulting in a decrease in structural accuracy. In this respect, experimental information from small-angle scattering of X-ray radiation in solution (SAXS) presents a suitable complement to the NMR data, as it provides an independent constraint on the overall molecular shape. A computational procedure is described that allows incorporation of such SAXS data into the mainstream high-resolution macromolecular structure refinement. The method is illustrated for a two-domain 177-amino-acid protein, gamma S crystallin, using an experimental SAXS data set fitted at resolutions from similar to 200 angstrom to similar to 30 angstrom. Inclusion of these data during structure refinement decreases the backbone coordinate root-mean-square difference between the derived model and the high-resolution crystal structure of a 54% homologous gamma B crystallin from 1.96 +/- 0.07 angstrom to 1.31 +/- 0.04 angstrom. Combining SAXS data with NMR restraints can be accomplished at a moderate computational expense and is expected to become useful for multidomain proteins, multimeric assemblies, and tight macromolecular complexes.