The presence of the plasma protein alpha 2HS-glycoprotein (alpha 2HS) has been demonstrated in the developing rat neocortex, using biotin-streptavidin immunocytochemistry. alpha 2HS was observed in the neocortex on embryonic day 20 but not earlier. At this age it was present in cells of the subplate and of the intermediate layer and in layer I anteriorly. Between postnatal day 5 and day 10 alpha 2HS-positive cells were found in greater number in various cortical layers and in fibres in layer I. At postnatal day 28 no alpha 2HS-positive cells or fibres could be found in the neocortex. alpha 2HS has been reported to be very closely related to fetuin which is a fetal plasma protein found in cells of the developing cortex in the sheep and the pig. It is suggested that these glycoproteins may be important in some aspects of early neocortical differentiation.