Increased intestinal permeability and the CD45RO isoform expression of the leukocyte common antigen on peripheral blood CD20+ B cells are found in Crohn's disease. Others have observed that multiple sclerosis (MS) patients may have an increased risk of coacquisition of Crohn's disease. The aim of this study was to identify an association between these diseases using peripheral blood CD45 isoform expression and intestinal permeability in MS. Lactulose/mannitol permeability and peripheral blood CD20+ B cell CD45RO expression were defined in healthy controls, MS patients, and patients coincidentally affected by MS and Crohn's or MS and ulcerative colitis (UC). Five of 20 MS patients had increased intestinal permeability, a finding not previously reported. High levels of CD45RO were found on circulating CD20+ B cells from patients with MS. This has not been reported previously in MS and is found in very few other conditions. Eight patients with coincident MS and Crohn's disease or MS and UC were studied. Coincident MS and UC patients expressed CD45RO on CD20+ B cells, a finding not identified in UC patients alone. A subgroup of MS patients has increased intestinal permeability. These patients express CD45RO CD20+ B cells, also found in Crohn's disease.