New 2-[(alpha-methylbenzylidene)hydrazino]benzoxazole derivatives have been synthesized by reacting ortho or para substituted acetophenones with 2-hydrazinobenzoxazole in ethanol. The structures of the synthesized compounds were confirmed by microanalysis, IR and NMR spectral data. Antimicrobial activities of the compounds were investigated by the microdilution susceptibility test in Mueller-Hinton broth and Sabouraud liquid medium. Test organisms: Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 as Gram (+) bacteria, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853 as Gram (-) bacteria, and Candida albicans, Candida stellatoidea, Candida parapsilosis and Candida pseudotropicalis as yeasts. Among the compounds tested 2-[(alpha-methyl-4-chlorobenzylidene)hydrazino]benzoxazole (compound 4) and 2-[(alpha-methyl-4-nitrobenzylidene)hydrazino] (compound 8) showed the most favorable activity.