Nestin is an intermediate filament protein that is predominantly expressed by progenitor cells during early CNS development. Its expression has been suggested to be most prominent during early gestation. However, contradictory results reporting nestin expression in the mature CNS have also been published. We wanted to investigate whether nestin is detectable in the CSF of newborn infants, and if so, whether this expression depends on gestational age and/or various cerebral diseases. Using western blot analysis and densitometry, we examined CSF samples from 20 newborn infants varying from 25 to 42 weeks of gestation. The infants suffered from perinatal asphyxia (n=7), periventricular leukomalacia and periventricular haemorrhage (n=6) and seven infants had no known cerebral disease (n=7). Protein extract from the periventricular brain tissue of a full-term 1-week old infant, who died from congenital heart disease, was also analyzed. Nestin was detected in all the CSF samples and also in the protein extract from brain tissue. A decrease in the relative nestin levels with increasing gestational age was found. There was no correlation between nestin levels and CNS injury. An unexpected finding was that brain-derived nestin had an apparent molecular weight of appx 240 kDa whereas all analysed CSF samples contained two nestin immunoreactive proteins at 200 and 220 kDa. Experimental deglycosylation of the 240 kDa form reduced its MW to 220 kDa, indicating that nestin undergoes a specific deglycosylation upon release into the CSF. The presence of nestin in the CSF and in the brain tissue suggest a population of nestin-positive stem cells in the brain at full-term gestation. The data do not support the use of nestin in the CSF as a marker for perinatal brain damage, but suggest nestin as a potential marker for neuronal progenitor cells.