Chemokines and their receptors are important in the trafficking of peripheral leukocytes into the central nervous system, a major event in the pathogenesis of multiple sderosis (MS). Evidence based on clinical, pathological and magnetic resonance imaging grounds supports some divergence between forms of MS with relapses [relapsing-remitting (RR) and secondary progressive (SP)] and the primary progressive (PP) form. To elucidate whether different pathogenic mechanisms are involved in PPMS, we compared membrane expression of a group of CC and CXC chemokine receptors (CCR1, CCR5, CXCR3, CXCR4) in peripheral blood of 68 MS patients (25 PPMS, 23 SPMS and 20 RRMS) and 26 healthy controls. We found a significant increase in surface expression of CCR5 in CD4+, CD8+, CD19+ and CD14+ cells as well as an increased percentage of CXCR3 and CXCR4 in CD14+ cells in MS patients compared to controls. Increased levels of CXCL10 (IP-10) and CCL5 (RANTES) in cerebrospinal fluid were also observed in a subgroup of MS patients. These results support that chemokines and their receptors are involved in the pathogenesis of MS However, a pattem of chemokine-chemokine receptor expression characteristic of each clinical form of the disease failed to be observed.