During the past year, we have been developing a diagnostic system to rapidly detect mutations in genes associated with drug resistance in M. tuberculosis. This system is based on the capacity of peptide-nucleic acid probes to efficiently discriminate between wild-type and mutated sequences. Using an ELISA format, we have shown that important point mutations in the katG gene can be detected using peptide-nucleic acid probes. We are currently trying to validate these procedures for identifying alterations in other M. tuberculosis genes associated with drug resistance.