Interleukin-10 (IL-10) is an anti-inflammatory cytokine that may be an important regulator in multiple sclerosis (MS) pathogenesis. IL-10 gene contains three single nucleotide polymorphisms (SNPs) and two polymorphic microsatellites in the 5'-flanking region. Our aim was to ascertain if any of these polymorphic markers is associated or linked to MS among Spanish patients. We have genotyped 300 patients and 357 ethnically matched controls for the microsatellites, and most of them also for the promoter SNPs. We included in this study the parents of 63 patients in order to perform a TDT analysis as well. IL-10G12 allele was significantly increased in MS patients (17% versus 11% in controls; p=0.004; p(c)<0.05). No other allele showed a significant difference between patients and controls, and the TDT analysis yielded negative results. The data indicate that IL-10 is not a major susceptibility locus in MS, but in our population it might, however, have a minor role.