Few histological studies have reported an increased of mast cells (MCs) in the brain of MS patients; we have therefore investigated whether this accumulation is associated with disease activity. We assessed a large series of post-mortem white matter samples from MS patients (n=59, 20 patients) and controls (n=28, 28 subjects) for MC-specific markers, such as FcepsilonRI, tryptase and chymase, using quantitative RT-PCR. We have found in MS samples a concordant and significant increase in MC markers and have confirmed the presence of MCs by immunohistochemistry. The levels of MC-specific transcripts showed a positive correlation with the increased levels of two potent MC chemoattractants, namely CCL5 and stem cell factor. The inflammatory stage of MS lesions had only a modest influence on MC accumulation. Our data point to an important patient-specific effect with regards to MC accumulation in MS brain. These observations indirectly suggest the implication of MCs in the pathophysiology of MS in a subset of patients.