Background: The chemokine receptor CXCR4 is linked to chemokine-mediated metastasis in breast cancer. The breast cancer microenvironment is rich in cytokines, known to have a regulatory effect on CXCR4. We examined the inflammatory cytokine regulation of CXCR4 surface expression and its effect on migration in MCF-7 and MDA MB231 cells. As heparin competitively antagonizes chemokines we evaluated its potential to block migration of these cell lines towards the chemokine SDF-1. Methods: Expression of CXCR4 was analysed by flow cytometry (R & D Mab 172) before and after stimulation with TNF-α or IFN-γ. The effects of TNF-α and heparin on migration were examined by chemotaxis assays. Results: TNF-α significantly reduced CXCR4 expression in both cell lines after 24 h (MCF-7: 83 per cent*; MDA MB231: 89 per cent*). In MCF-7 cells IFN-γ reduced expression (97 per cent*) by 24 h; a bi-phasic response was observed for MDA MB 231 cells, with a maximal reduction occurring after 16 h (83 per cent*), returning to unstimulated levels by 24 h. The reduction in CXCR4 expression by TNF-α was consistent with reduced migration towards SDF-1 (MCF-7 by 80 per cent*, MDA MB231 by 94 per cent*). Heparin also inhibited chemotaxis of MCF-7 (at 250 µg mL−1*) and MDA MB231 (at 100 µg mL−1 and 250 µg mL−1*). Conclusions: Regulation of the CXCR4 by proinflammatory cytokines alters the ability of breast cancer cells to migrate towards SDF-1. Heparin significantly reduces SDF-1 induced breast cancer cell migration, suggesting a potential therapeutic action in patients with breast cancer. Statistics: Student's one-tailed t-test. (*P < 0.05) (TNF-α: tumour necrosis factor alpha, IFN-γ: interferon gamma, SDF-1: stromal derived factor-1)