Motivation: Chemical cross-linking of proteins or protein complexes and the mass spectrometry-based localization of the cross-linked amino acids in peptide sequences is a powerful method for generating distance restraints on the substrate's topology.Results: Here, we introduce the algorithm Xwalk for predicting and validating these cross-links on existing protein structures. Xwalk calculates and displays non-linear distances between chemically cross-linked amino acids on protein surfaces, while mimicking the flexibility and non-linearity of cross-linker molecules. It returns a ‘solvent accessible surface distance’, which corresponds to the length of the shortest path between two amino acids, where the path leads through solvent occupied space without penetrating the protein surface.Availability: Xwalk is freely available as a web server or stand-alone JAVA application at http://www.xwalk.org.Contact: abdullah@imsb.biol.ethz.ch; aebersold@imsb.biol.ethz.chSupplementary information: Supplementary data are available at Bioinformatics online.