The activity of the Golgi glycosyltransferase beta1,6 N-acetylglucosaminyltransferase (core 2 GlcNAc-T), which plays a role in T-cell activation and cell-cell adhesion, appears to be modulated in resting lymphomonocytes during different phases of multiple sclerosis (MS). In particular, a significant decrease (25-30%) of the enzyme activity was observed, with respect to healthy subjects, in MS patients who were in relapse or in the very early stages of remission. A similar trend was found to be associated with patients affected by active lesions. A statistically significant decrease in the enzyme activity was also observed in patients with the progressive form. By contrast, core 2 GlcNAc-T activity did not appear correlated with duration of the disease. Interestingly, MS individuals under treatment with IFN-beta1a, an immunosuppressive agent, showed levels of activity which were comparable with those observed in healthy subjects. Together, these observations suggest that down-regulation of core 2 GlcNAc-T activity is linked to the occurrence of acute phases in the relapsing-remitting form and to the progressive form of the disease, probably caused by altered expression of glycoproteins which are involved in lymphomonocyte activation and/or interaction with the endothelium. Additionally, it appears that the enzyme assay may provide a useful marker of the disease activity and the effects of therapeutical approaches.