Derivatives of mycaminosyl tylonolide (1) and 4'-deoxymycaminosyl tylonolide (2) containing N-ethyl-2-fluoro-, 2,2-difluoro- and 2,2,2-trifluoroethylamino groups at their C-23 have been prepared by treating 23-deoxy-23-ethylaminomycaminosyl tylonolide diethyl acetal (14) and its 4'-deoxy analog 15 with 2-fluoro-, 2,2-difluoro- and 2,2,2-trifluoroethyl trifluoromethanesulfonates. The relationship between the antibacterial activity and the numbers of the fluorine atoms introduced in the final products is discussed.