The development of the folliculo-stellate cell in human fetal pituitaries has been investigated by immunocytochemical methods for S-100 protein and glial fibrillary acid protein. S-100 positivity was first observed in pars intermedia cells in a 13-week fetus. Staining with this antiserum is seen in cells of the pars distalis after 15 weeks. Glial fibrillary acid protein was not apparent until 18 weeks, when only cells in the pars intermedia were stained. These cells were not seen in the pars distalis before 28 weeks' gestation, but were present in a 39-week specimen and in a 5 day old baby. In most pituitaries examined, cells staining for S-100 and glial fibrillary acid protein were more concentrated in the pars intermedia than the pars distalis. These results suggest that folliculo-stellate cells in the human pituitary originate in the neurally associated facet of the pars intermedia and pass through this lobe to reach the pars distalis. Since these cells stain for glial related antigens, they may be a modified form of glial cell and arise in the neuroectoderm. Evidence for this hypothesis is given by a lack of both S-100 and glial fibrillary acid protein in the pituitaries of three anencephalic pituitaries. Differences in the timing of S-100 and glial fibrillary acid protein immunoreactivity may be related to either developmental aspects of the folliculo-stellate cell, or to the presence of two distinct cell types.