In cultured astroglia, cysteamine induces the accumulation of peroxidase-positive cytoplasmic inclusions in the context of a generalized cellular stress response. In the present study, systemic cysteamine administration over a 3 week period induced HSP27, 72, 90, and GRP94 (stress proteins) in astrocytes and significantly increased numbers of peroxidase-positive astrocytic inclusions in the various brain regions relative to controls. Similar patterns of HSP expression were also observed at 24 hours following cysteamine treatment indicating that cellular stress may be a very proximal event in the biogenesis of the astrocytic inclusions. The topography of glial peroxidase activity may provide a "map" of central nervous system regions particularly prone to oxidative stress during normal aging and under pathologic conditions.