The PM3 and B3LYP methods were employed to calculate the properties of 18 7-substituted fluoroquinolones.The correlation between biological activity (against gram-positive organisms or gram-negative organisms) and structural properties was obtained by using multiple linear regression (MLR) methods.The best model generated correlates the antibacterial activity with EHOMO and QF8 for gram-positive organisms,and EHOMO and dipole moment for gram-negative organisms,respectively.It suggests that the interaction mechanisms of fluoroquinolons with gram-positive and gram-negative organisms are different.