Polymorphic microsatellite markers in the genes for gelatinase B, PECAM-1 and MCP-3 have previously been analysed in Swedish and Sardinian individuals to test for association with multiple sclerosis (MS). Confirmation and comparison of genetic associations in various ethnic populations is mandatory and, therefore, we studied these three gene polymorphisms in 216 clinically definite MS patients and 193 normal controls, and in 148 simplex MS families, all of Belgian origin. No allelic associations were found between MS and the CA microsatellite marker in the promoter region of the gelatinase B gene, and the polymorphic CA repeat in the sixth intron of PECAM1. However, the two most abundant alleles of the CA/GA microsatellite polymorphism in the promoter-enhancer region of the MCP-3 gene, A2 (109 bp) and A3 (111 bp), were found to be significantly associated with disease in the case-control study [OR (95% CI)=0.68 (0.51-0.92), p (1 df)=0.015 and OR (95% CI)=1.62 (1.22-2.14), p (1 df)=0.0010, respectively], but not in the family study. These results are in agreement with previous findings in the Swedish and Sardinian populations and reinforce the possibility of a role for chemokines in MS pathogenesis.