Biological processes are commonly controlled by precise protein-protein interactions. These connections rely on specific amino acids at the binding interfaces. Here we predict the binding residues of such interprotein complexes. We have developed a suite of methods, i-Patch, which predict the interprotein contact sites by considering the two proteins as a network, with residues as nodes and contacts as edges. i-Patch starts with two proteins, A and B, which are assumed to interact, but for which the structure of the complex is not available. However, we assume that for each protein, we have a reference structure and a multiple sequence alignment of homologues. i-Patch then uses the propensities of patches of residues to interact, to predict interprotein contact sites. i-Patch outperforms several other tested algorithms for prediction of interprotein contact sites. It gives 59% precision with 20% recall on a blind test set of 31 protein pairs. Combining the i-Patch scores with an existing correlated mutation algorithm, McBASC, using a logistic model gave little improvement. Results from a case study, on bacterial chemotaxis protein complexes, demonstrate that our predictions can identify contact residues, as well as suggesting unknown interfaces in multiprotein complexes. Proteins 2010. © 2010 Wiley-Liss, Inc.