The myxovirus resistance A (MXA) mRNA has been extensively investigated for assessing the biologic responses of multiple sclerosis (MS) patients to interferon-beta (IFN-beta) therapy. The objective of this study was to evaluate the associations between two MXA promoter region single nucleotide polymorphisms (rs2071430 and rs17000900) and the gene expression responses, clinical and MRI phenotypes in IFN-beta treated MS patients. The rs2071430 and rs17000900 SNPs, which are located in or near an interferon-stimulated response element (ISRE), were genotyped in 179 relapsing MS patients. Quantitative MRI measurements were available for 101 patients on IFN-beta monotherapy. Gene expression was assessed in 22 anti-interferon-beta neutralizing antibody negative patients. No significant association was found between the MXA genotype at these two SNPs and clinical, MRI and MXA gene expression in MS patients treated with IFN-beta therapy.