It was shown that the mechanism of action of minocycline on intact cells of E. coli was similar to that of oxytetracycline, i.e. specific inhibition of protein synthesis. In acellular systems of synthesis of polyphenylalanine with ribosomes from tetracycline sensitive and resistant strains of E. coli, minocycline and oxytetracycline had close inhibiting activity. Therefore, the highest antimicrobic activity of minocycline was due as compred to oxytetracycline to some advantages at the stage of penetration into the microbial cell and not at the stage the protein synthesis. 4-Epi-oxytetracycline and beta-apo-oxytetracycline possessing competing properties with respect to oxytetracycline at the stage of penetration through the cell membrane did not, however, suppress the synthesis of polyphenylalanine in the acellular system isolated from the sensitive strain of E. coli.