Chloropeptins I and II, which are gp120-CD4 binding inhibitors, were isolated as pale yellow-brown powders from the mycelia of a soil actinomycete, Streptomyces sp. WK-3419. Their physico-chemical properties showed that they are chlorinated peptides. Chloropeptin I (C61H45N7O15Cl6) is a novel compound, but chloropeptin II was identified as complestatin. Both compounds inhibited gp120-CD4 binding (IC50: 1.3 and 2.0 μm, respectively), the cytopathic effect of HIV in MT-4 cells (EC50: 1.6 and 1.7 μM, respectively) and syncytium formation in co-cultured HIV-1-infected and uninfected MOLT-4 cells (IC50: 0.5 and 1.1 μm, respectively). Chloropeptin I was synergistic in the inhibition of the cytopathic effect when combined with other anti-HIV drugs. Here, we report additional two gp120-CD4 binding inhibitors, chloropeptins I and II, produced by Streptomyces sp. isolated from a soil sample. This paper describes the taxonomy, fermentation, isolation, physico-chemical properties and biological activities of these compounds, a preliminary account of which was published in this journal. The structure elucidation will be separately reported.