Segmented normal-appearing brain tissue (NABT) was investigated in 40 patients with a recent onset and 13 patients with a remote onset of a clinically isolated syndrome (CIS) using magnetization transfer ratio (MTR) histograms. Abnormalities were present in patients with a high risk for MS (recent onset and T2-weighted lesions present) and in those with a low risk for relapse (recent onset without T2-weighted lesions). Similar mild NABT abnormality was present with CIS and no further disease activity 14 years later. NABT MTR abnormality in CIS may indicate susceptibility to demyelination but not to disease progression.