A series of twenty-one 7-chloro-4-quinolinylhydrazones (3a-u) have been synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H(37)Rv. The compounds 3f, 3i and 3o were non-cytotoxic and exhibited an important minimum inhibitory concentration (MIC) activity (2.5 microg/mL), which can be compared with that of the first line drugs, ethambutol (3.12 microg/mL) and rifampicin (2.0 microg/mL). These results can be considered an important start point for the rational design of new leads for anti-TB compounds.