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This paper describes a multiple-defect diagnosis methodology that is flexible in handling various defect behaviors and arbitrary failing pattern characteristics. Unlike some other approaches, the search space of the diagnosis method does not grow exponentially with the number of defects. Results from extensive simulation experiments and real failing integrated circuits show that this method can effectively diagnose circuits that are affected by a large (>20) or small number of defects of various types. Moreover, this method is capable of accurately estimating the number of defective sites in the failing circuit.