From our quantitative structure-activity relationship (QSAR) study on a large set of 6-aminoquinolones, which indicated that a group larger than methyl could be allocated at C-8 position, we have synthesized two new series of 6-aminoquinolones characterized by the presence of an ethyl or a methoxy group at C-8 position. The antibacterial evaluation shows that, while the 8-ethyl derivatives were devoid of any antibacterial activity, the introduction of methoxy group gave compounds with good antibacterial activity, especially against gram-positive bacteria. A tentative explanation of the different behaviours among the 8-substituted analogues is given taking into account both the length and electronic properties of the C-8 groups.