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Current diagnostic tests for tuberculosis based on tuberculin have poor specificity, and both BCG vaccination and exposure to non-tuberculosis mycobacteria produce a response similar to that induced by infection with Mycobacterium tuberculosis. The identification of regions of the M tuberculosis genome that are not present in BCG and non-tuberculous mycobacteria provides a unique opportunity to develop new highly specific diagnostic reagents. We describe the current status of attempts to exploit this information and summarise recent research that has used defined antigens for an accurate and rapid test for tuberculosis infection based on the detection of T cells sensitised to M tuberculosis either by blood tests in vitro or skin tests in vivo.