Background: Chemokines, small chemotactic cytokines, have been implicated in active relapsing-remitting MS (RRMS). However, the role of chemokines and chemokine receptors has not been specifically studied in secondary progressive MS (SPMS). Methods: Fifteen patients with SPMS, 15 patients with relapses of RRMS, 10 patients with RRMS in remission, and 20 healthy controls were included in this study. The expression of CC chemokine receptor 1(CCR1), CCR2, CCR3, CCR5, and CXC chemokine receptor 3(CXCR3) was studied on leukocyte subsets using flow cytometry, and the cytokine profile of T cells expressing CCR2 and CCR5 was determined. The authors also studied the effect of treatment with interferon-β-lb on the expression of chemokine receptors in SPMS. Results: The authors found a significantly higher percentage of CCR2-expressing T cells in SPMS than in the other patients groups. CCR2-positive T cells produced high levels of interleukin (IL)-5 and low levels of tumor necrosis factor α, indicating a T-helper type 2 (Th2)/T-cytotoxic type 2 (Tc2) profile of these cells. The expression of CCR5, a chemokine receptor associated with Th1 responses, was significantly lower in SPMS than in patients with active RRMS. Interferon (IFN) β-1b treatment in SPMS did not alter chemokine receptor expression in SPMS. Conclusion: The authors find qualitative differences in the systemic inflammatory response in RRMS and SPMS, indicating a distinct inflammatory environment in SPMS. Chemokine receptor expression in SPMS did not change after treatment with IFNβ-1b. It remains to be established if these findings reflect differences between RRMS and SPMS in effector or regulatory mechanisms.