The crystal structure of a soluble form of Borrelia burgdorferi outer surface protein A (OspA) complexed with the Fab fragment of a monoclonal antibody has revealed an unusual structure that has a repetitive antiparallel beta topology with a nonglobular, single layer beta-sheet connecting the globular N- and C-terminal domains. Earlier NMR studies have shown that the local structure of OspA including the single layer beta-sheet is similar to the crystal structure. Here we report a small angle X-ray scattering (SAXS) study of the global conformation of OspA in solution. The radius of gyration (Rg) and the length distribution function (P(r)) of OspA measured by SAXS in solution are nearly identical to the calculated ones from the crystal structure, respectively. The NMR and SAXS experiments complement each other to show that OspA including the central single-layer beta-sheet is a stable structure in solution, and that the OspA crystal structure represents the predominant solution conformation of the protein.