CCR5 is the receptor for CC chemokines MIP-1alpha, MIP-1beta, and RANTES, and is preferentially expressed on Th1 lymphocytes. CCR5 is a coreceptor for macrophage-tropic HIV, and its ligands potently inhibit HIV replication in human leukocytes. In addition, HIV-infected patients with the nonfunctional CCR532 allele exhibit delayed onset of AIDS symptoms, and pharmacological antagonism of CCR5 inhibits HIV-1 infection. Preclinical testing of small molecule antagonists of CCR5 has been hampered by low affinity of the compounds to rodent and dog CCR5, but two such compounds, maraviroc and AD101, have been shown to have potent antagonist activity at rhesus macaque CCR5, which differs from human CCR5 by 8 amino acids. One antagonist of human CCR5, SCH-C, does not block HIV entry through rhesus macaque CCR5, and one amino acid difference is responsible for the functional difference.