R5 HIV replicated in freshly isolated human peripheral blood monocytes after treatment with 1-methyladenosine (fresh PBM/MA), an immunosuppressive compound isolated from tumorous ascites fluids, while viral replication was not demonstrated in untreated peripheral blood monocytes (fresh PBM). The R5 HIV replication in fresh PBM/MA was inhibited by glycyrrhizin (GL). Without any other stimulation, fresh PBM/MA produced CCL2 and IL-10, while these soluble factors were not released from fresh PBM. GL greatly inhibited the production of CCL2 and IL-10 in fresh PBM/MA. After treatment with CCL2 and/or IL-10, CCR5 mRNA expression in fresh PBM was markedly enhanced, while only a trace level of the mRNA expression was detected in these cells in the absence of CCL2 or IL-10. CCR5 mRNA expression in fresh PBM treated with CCL2 or IL-10 was clearly inhibited by GL. These results indicate that GL inhibits R5 HIV replication in fresh PBM/MA through the inhibiting CCR5 expression mediated by CCL2 or IL-10.