We present a Web-based application that uses whole-protein masses determined by mass spectrometry to identify putative co- and posttranslational proteolytic cleavages and chemical modifications. The protein cleavage and modification engine (PROCLAME) requires as input an intact mass measurement and a precursor identification based on peptide mass fingerprinting or tandem mass spectrometry. This approach predicts mass-modifying events using a depth-first tree search, bounded by a set of rules controlled by a custom-built fuzzy logic engine, to explore a large number of possible combinations of modifications accounting for the experimental mass. Candidates are saved during a search if they are within a user-specified instrument mass accuracy; the total number of possible candidates searched is based on a specified fuzzy cutoff score. Candidates are scored and ranked using a simple probabilistic model. There is generally not enough information in an intact mass measurement to determine a single unique protein characterization; however, the program provides utility by expediting the identification of sets of putative events consistent with the mass data and ranking them for further investigation. This approach uses a simple, intuitive rule base and lends itself to discovery of unannotated posttranslational events. We have assessed the program with both in silico-generated test data and with published data from an analysis of large ribosomal subunit proteins, both from the yeast S. cerevisiae. Results indicate a high degree of sensitivity and specificity in characterizing proteins whose masses resulted from reasonable proteolysis and covalent modification scenarios. The application is available on the web at http://proclame.unc.edu.