The orally active fluoroquinolone antiinfectives, represented generically by 1 and 2 in Figure 1, have generated much excitement in laboratories and clinics around the world. The earliest entries into this class of agents were enoxacin (1a), norfloxacin (1b), pefloxacin (1c), and ofloxacin (2a), all of which contain a piperazinyl moiety for R7 and a two-atom fragment for R1. Many new R1 substituents have been reported with the halophenyl (difloxacin, 1d) and cyclopropyl (ciprofloxacin, 1e) among the most successful modifications. Structure-activity studies in these laboratories involving the 7- and 8-positions of the 4-quinolone (R7 and X) have demonstrated that amino-substituted pyrrolidines were efficient mimics of the piperazine side chain, and they conferred remarkable improvements in the Gram-positive (Staphylococci and Streptococci) antibacterial potency in vitro. A fluorine atom was desirable at C8 (X = F) for optimal in vivo efficacy (CI-934, 1f, and PD 117,558, 1g). All of these agents and several of the earliest quinolones have been evaluated side by side for their antibacterial activity and their inhibition of the target enzyme, DNA-gyrase. Although a few examples of 5-substituted quinolones, such as 5-halo, 5-alkyl and an 8-amino version (2b) of ofloxacin have been reported, no systematic structure-activity relationship has been developed. Some reports have even suggested that substitution at the 5-position was deleterious to antibacterial activity. As part of our continuing efforts in utilizing the optimized fragments described above, we have discovered that, contrary to previous reports, an amino function at the 5-position of the 6,8-difluoro-1-cyclopropylquinolone significantly enhances antibacterial potency while displaying some intriguing physical characteristics. In this communication we describe the synthesis and biological activity of a series of 5-amino-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids appended with piperazine (3) or pyrrolidine (4) side chains and their comparison to known reference agents.