In a prospective sample of patients with multiple sclerosis (MS) we found a high frequency of antinuclear antibodies (ANA), 22.5%, confirming results from previous studies. ANA occurrence did not correlate with gender, age, duration of MS, MS course, or disability in either the prospective and retrospective samples of MS patients. In 16 patients with MS tested at two time points, ANA occurrence did correlate with MS disease activity. This suggests that the high frequency of ANA in MS reflects ongoing immune dysregulation.