In the present study, we found that the soluble D1D2 molecule could enhance infectivity of a CCR5-using HIV-1 strain Bal in Cf2Th-CCR5 (CD4-/CCR5+) cells at the concentration from 5 to 200 nM, while 2DLT and T1144 exhibited no enhancement of HIV-1 infection at the same concentration range. Here, CD4 is linked to HIV-1 infection.