The small heat shock protein αB-crystallin was recently identified as a dominant human T-cell antigen in myelin derived from multiple sclerosis (MS) patients. Using immunohistochemical techniques, oligodendrocytes as well as astrocytes in MS lesions were shown to express α B-crystallin. In the present study we examined the expression of α B-crystallin, human natural killer cell marker (HNK-1; as a marker for immature oligodendrocytes) and heat shock protein 60 (hsp60) in gila cells at different stages of MS lesion development i.e. in early active lesions; late active lesions and inactive lesions. The results demonstrate that already at the earliest stages of lesional development a subpopulation of oligodendrocytes express detectable levels of αB-crystallin. In active lesions about 5-10% of all oligodendrocytes were found to express αB-crystallin, whereas in inactive lesions the relative number of αB-crystallin-expressing oligodendrocytes was approximately tenfold less. For astrocytes the relative number of αB- crystallin-expressing cells was 40-50% for all three types of lesions. Also, αB-crystallin-expressing oligodendrocytes and astrocytes displayed different patterns of distribution in lesional areas. These data suggest different regulatory pathways for αB-crystallin expression in either type of glia cell. No correlation was found between expression patterns of HNK-1 and αB- crystallin indicating that the subpopulation of αB-crystallin-expressing oligodendrocytes consisted of both mature and immature oligodendrocytes. In addition, no correlation was found between expression of hsp60 and αB- crystallin in MS lesions suggesting different regulatory pathways for either hsp.