T lymphocytes and macrophages probably play a role in the pathogenesis of multiple sclerosis (MS), and migration of these cells into the central nervous system is facilitated by disruption of the capillary basement membrane. Laminin is a major extracellular matrix of the basement membrane. To investigate whether ability of lymphocytes to degrade laminin correlates with disease activity in MS, we conducted a prospective study in consecutive 24 MS patients. A novel quantitative assay was developed to estimate the ability of peripheral blood mononuclear cells (PBMCs) to degrade laminin. The assay was performed every four weeks over a period of 12 months. During the study period, a total of 41 relapses were observed. The ability to degrade laminin was significantly higher in MS patients, even during clinical remission, than in normal and neurological controls, and was transiently increased further within 4 weeks before relapse (p=0.076). In MS, the ability of peripheral blood lymphocytes to degrade laminin increases, and may correlate with disease activity.