Cross-validation of a solid-state NMR-derived membrane polypeptide structure is demonstrated. An initial structure has-been achieved directly from solid-state NMR derived orientational restraints based on a variety of anisotropic nuclear spin interactions. Refining the molecular structure involves setting up a penalty, function that incorporates all available solid-state NMR experimental data and an energy function. A validation method is required to choose the optimal weighting factor for the total penalty function to balance the contribution from the experimental restraints and. the energy function. Complete cross-validation has been used to avoid over-fitting the orientational restraints. Such cross-validation involves partitioning of the experimental data into a test set and a working set followed by checking the free R-value during the refinement process. This approach is similar to the method used in crystallography and solution NMR. Optimizing the weighting factor on the penalty function by cross-validation will increase the quality of the refined structure from solid-state, NMR data. The complete cross-validation and R-factor calculation is demonstrated using experimental solid-state NMR data from gramicidin A, a monovalent cation channel in lipid bilayers.