In the present study we searched for an association between the human endogenous retroviral element HRES-I and multiple sclerosis (MS). Fragments of this endogenous retrovirus were amplified for subsequent examination by single strand conformational analysis. We did not find HRES-I markers exclusively linked with MS and only the two already known polymorphisms, which define three alleles of HRES-I, were detected. However, we found a significant difference in the distribution of these alleles between a group of 87 MS patients and a control group of 158 healthy individuals (P=0.014). There were no differences in the distribution of the HRES-I allelic forms between MS patients with a relapsing-remitting course and patients with chronic progressive MS. Our results provide evidence of an association between HRES-I and MS. Possible explanations for this are discussed.