In neonatal mice, an acute injury produced by a stab wound to the cortex results in minimal astrocyte reactivity, as has been observed by others. However, if the source of the stab wound, a piece of nitrocellulose (NC) membrane, were now implanted in the cortex for a period of time (chronic NC implant injury), then extensive astroglial reactivity in the neonatal brain ensues. The astrogliosis is manifested by increased mRNA, protein content, and immunoreactivity for GFAP, and by ultrastructural changes. Given the previous reports that inflammatory cytokines are possible mediators of astrocyte reactivity (e.g., Balasingam et al: J Neurosci 14:846, 1994), we examined the brain parenchyma of neonatal mice following an NC stab or implant injury, with minimal or extensive astrogliosis, respectively, for a possible differential representation of inflammatory cells. A significant correlation (r = 0.87, P < 0.05) was observed between the occurrence of astrogliosis and the presence of reactive microglia/macrophages; no other inflammatory cell type was detected in the brain parenchyma of neonatal mice following NC implant injury. We suggest that reactive microglia/macrophages are required for the evolution of cells into reactive astrocytes following insults to the neonatal brain.