New N-2-cycloalkylidene-(6-phenyl/4-chlorophenylimidazo [2,1-b] thiazol-3-yl) acetic acid hydrazides (2a-h and 3a-b) were synthesized by reacting (6-phenyl/4-chlorophenylimidazo[2,1-b] thiazol-3-yl) acetic acid hydrazides with cyclohexanones or cyclopentanone. Furthermore, 2a-h were refluxed with thioglycolic or thiolactic acid to give 4-[[(6-phenyl/4-chlorophenylimidazo [2,1-b] thiazol-3-yl) acetyl]amino]-4-aza-1-thiaspiro[4.5]decan-3-ones (4a-h and 5a-h). The structures of the tide compounds were established by spectral data (IR, H-1-NMR, C-13-NMR and EIMS (Electron Impact Mass Spectrometry)) and elemental analysis. The synthesized compounds were evaluated for antituberculosis activity against Mycobacterium tuberculosis H(37)Rv (ATCC 27294). The compounds exhibited varying degrees of inhibition in the in vitro primary screening that was conducted at a concentration of 6.25 mug/ml against M. tuberculosis H(37)Rv (ATCC 27294) in Bactec 12B medium using the Bactec 460 radiometric system or a broth microdilution assay, the Microplate Alamar Blue Assay (MABA). Compounds 2f, 2h, 3b, 4a, 4c, 4d, 5a-e and 5h demonstrating at least 90% inhibition in the primary screen were re-tested at lower concentrations against M. tuberculosis H37Rv (ATCC 27294) to determine the actual minimum inhibitory concentration (MIC) using MABA. The most active compounds were found to be 4d and 5c. The structure-activity relationships of the derivatives were investigated.