BACKGROUND: An association of two single-nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) gene, Apal (rs7975232) and Taql (rs731236), with multiple sclerosis (MS) has been reported in a Caucasian population. Another SNP of the VDR gene, Fokl (rs10735810), has been associated with serum levels of 25-hydroxyvitamin D [25(OH)D]. OBJECTIVE: Since 25(OH)D status has been associated with MS incidence, we assessed the association Apal and Taql with the serum levels of 25(OH)D and 1,25(OH)(2)D, and MS in our population. METHODS: We determined the two SNPs as well as the summer and winter period serum levels of 25(OH)D and 1,25(OH)(2)D in 212 MS patients. Additionally, we genotyped 289 healthy controls and determined the metabolite levels. RESULTS: The genotype and allele distribution of the two VDR gene SNPs did not differ between patients and controls. There was no association of the Apal and Taql SNPs with 25(OH)D levels, 1,25(OH)(2)D levels, or 1,25(OH)(2)D/25(OH)D ratios in patients or controls. DISCUSSION: We found no association of the Apal and Taql VDR gene SNPs with MS or with vitamin D metabolism in our population. Further research should assess the complex interaction between vitamin D, the VDR, and susceptibility to MS.