CXCR4 is a G-protein coupled receptor for the chemokine CXCL12 (SDF-1), which is involved in cell migration and proliferation. It is also a co-receptor used by the X4 strains of HIV, which predominate at later stages of infection, and is required for their entry into target cells. We are designing and synthesizing non-peptide small molecule inhibitors of CXCR4 based on modeling studies. Lead compounds that compete with known CXCR4 antagonists, such as the peptide T-140, are being investigated for their ability to inhibit HIV infection in vitro, and to inhibit tumor cell metastasis in vitro and in a mouse model.