Glial fibrillary acidic protein (GFAP) is the structural protein of intermediate filaments in astroglia. GFAP has extensively been used as a marker of gliosis in neuropathology. It also appears in excessive amounts in the cerebrospinal fluid in various acute brain disorders. Hypoxic-ischemic encephalopathy after perinatal asphyxia is a condition in which levels of GFAP could be expected to be elevated if brain cell damage occurs. We examined levels of GFAP by a sensitive ELISA in the cerebrospinal fluid of full-term infants between 12 and 48 h after birth. Cerebrospinal fluid-GFAP increased 5-fold in infants after perinatal asphyxia compared with a reference group (675 versus 137 ng/L, p < 0.001). The levels of GFAP also increased gradually in accordance with the severity of the neurologic symptoms ranked as degree of hypoxic-ischemic encephalopathy. We conclude that the cerebrospinal fluid levels of GFAP might be an important adjunct in the neonatal assessment of infants subject to perinatal asphyxia, and together with other neuronal or glial proteins, it might also help in defining temporal relationships in asphyxia.