Six neurohypophysial GCTs and 31 normal neurohypophysis were studied by immunohistochemical techniques. The latter were grouped into A (< 5 yr old), B (30-49 yr), and C (> 70 yr). GCTs were all labeled by PNA. and some showed reactivity for S-100 protein, AAT, AAC, and cathepsin B. In addition, some were oxytocin- and vasopressin-positive. Unlike extracranial GCTs, neuron-specific enolase, myelin basic protein, and vimentin were not detected. Glial fibrillary acidic protein, keratin, and desmin were also not observed. In contrast, a few cells of the normal neurohypophysis showed immunoreactivity for AAT, AAC, cathepsin B, and PNA, similar to the cells of GCT. These cells tended to increase in number with age: group A showed fewer cathepsin B-positive cells than groups B and C (p < 0.001). These results show that neurohypophysial GCTs have some features that differentiate them from extracranial GCTs, for which a Schwann cell origin has been proposed by many authors. It was concluded that neurohypophysial GCT may originate from the cells that showed similar immunoreactivity, the ''granular'' pituicytes. Our results also support the hypothesis that neurohypophysial GCTs are an age-related metabolic disorder of lysosomes rather than true neoplasms.