Populations with insufficient ultraviolet exposure and who consume diets low in vitamin D have low vitamin D status (plasma 25-hydroxyvitamin D (25(OH)D) concentrations) and a reported higher incidence of multiple sclerosis (MS). The active form of vitamin D, 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), is an effective anti-inflammatory molecule. No research to date has assessed 1,25(OH)₂D₃ concentrations in individuals with MS. In this study, plasma concentrations of 25(OH)D, 1,25(OH)₂D ₃ and parathyroid hormone (PTH) were measured in 29 individuals with MS and 22 age- and sex-matched control volunteers. There were no significant differences in plasma PTH, 25(OH)D and 1,25(OH)₂D₃ concentrations between individuals with MS and control volunteers. Women with MS had significantly higher 25(OH)D and 1,25(OH)₂D₃ concentrations than men with MS (79.1 ±45.4 versus 50.2±15.3 nmol/L, P=0.019 and 103.8± 36.8 versus 70.4±28.7 pmol/L, P=0.019, respectively). There was a significant positive correlation between 25(OH)D and 1,25(OH)₂D ₃ concentrations in all subjects (r=0.564, P=0.000), but secondary analysis revealed that the correlation was driven by women with MS (r=0.677, P= 0.001). Significant sex differences in vitamin D metabolism were observed and were most marked in individuals with MS, suggesting that vitamin D requirements may differ between the sexes, as well as by underlying disease state. Multiple Sclerosis 2007; 13: 670-672. http://msj.sagepub.com