Polymorphisms in chemokine receptor CCR5 genes have been implicated in HIV disease progression, resistance, or non-progressive infection. Multiple CCR5 transcripts and mRNA diversity have also been identified. This study presents evidence to show that two distinct forms of CCR5 protein, 62 and 42k Da, are present in human lymphocytic cells and monkey peripheral blood mononuclear cells. The ratio of these two forms of CCR5 changes with cell growth. The 62k Da CCR5 predominates if the electrophoresis sample buffer does not contain reducing agent. However, the 62 and the 42 kDa CCR5 are not interconvertible. Morphine sulfate induces the formation and expression of both forms of CCR5 whereas RANTES, MIP-1alpha or MIP-1beta inhibits them. Localization studies indicate that the 62 kDa CCR5 resides mainly on the cell membrane and the 42 kDa CCR5 is present solely in the cytoplasm of the cells.