Objective - To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with β-interferon (IFN-β). Methods - The CCR5 Δ32 allele and a CCR5 promoter polymorphism associated with cell surface expression of CCR5 were analyzed in 109 patients with relapsing-remitting MS treated with IFN-β who were followed clinically for 1 year. Cellular CCR5 expression was measured by flow cytometry. Results - Patients with MS had a higher percentage of CCR5-positive monocytes than healthy controls. Increased monocyte expression of CCR5 correlated weakly with an increased short-term relapse risk but there was no relationship between CCR5 Δ32 allele and CCR5 promoter polymorphism genotypes and relapse risk. Conclusions - The results do not support a major role of CCR5 in the pathogenesis of relapses in MS patients treated with IFN-β, but it is possible that monocyte CCR5 expression may be used as a marker of disease activity.