Heat shock proteins (HSP) have been implicated in the interactions between the gammadelta T lymphocyte population and target tissues. Gammadelta T cells are found in increased numbers in multiple sclerosis (MS) plaques compared to their proportion in peripheral blood, co-localizing with oligodendrocytes (OGC) expressing HSP. We have demonstrated that such gammadelta T cells can induce in vitro lysis of human adult-derived OGC. Using immunohistochemical and flow cytometry techniques, we examined the constitutive and/or inducible expression of HSP in or on adult human-derived glial cell cultures in vitro. HSP70 was expressed in OGC maintained at basal temperature, but the expression of the inducible HSP70 protein was upregulated by a prior 43-degrees-C heat exposure. HSP70 could not be detected within astrocytes (GFAP+ cells), whether heat stress was applied or not. Constitutive expression of HSP60 could be discerned on the surface of all OGC under non-stressed culture conditions. Only some astrocytes demonstrated minor punctate surface HSP60 staining, whereas the remainder did not express HSP60 constitutively. These observations raise the possibility that OGC, by virtue of their differential expression of HSP compared to other glial cells, may be particularly prone to interaction with HSP-reactive gammadelta T cells. Such findings may further implicate gammadelta T cells in the pathogenesis of MS, a putative autoimmune disease in which immune-mediated injury is directed specifically against the oligodendrocyte-myelin unit within the central nervous system.