The present study shows that under glucose-deprived conditions immunostimulated astrocytes rapidly undergo death due to their increased susceptibility to endogenously produced peroxynitrite. Fe(III)tetrakis(N-methyl-4'-pyridyl)porphyrin (FeTMPyP), but not the structurally related compounds ZnTMPyP and H(2)TMPyP, prevented the death in glucose-deprived immunostimulated astrocytes. Consistently, FeTMPyP, not ZnTMPyP and H(2)TMPyP, completely blocked the elevation of nitrotyrosine immunoreactivity (a marker of peroxynitrite) and the depolarization of the mitochondrial transmembrane potential in glucose-deprived immunostimulated astrocytes. The present data suggest that peroxynitrite may be associated with glial cell death during metabolic deterioration in the cerebral ischemic penumbra.