The immunoreactivity of a panel of poly- and monoclonal antibodies raised against different neuronal and glial antigens, was studied in paraffin-embedded specimens of five pineocytomas. Antibodies against neuron-specific enolase (NSE), S-100 protein, neurofilaments protein (NFP), glial fibrillar acidic protein (GFAP), myelin basic protein (MBP), Synaptophysin (SYN) and vimentin were used. NSE immunoreactivity was detectable in nearly all tumoral cells. S-100 expression was present in all tumors, but a significant variation in the number of S-100 positive cells was noted in the different specimens; they ranged from 3% of S-100 positive cells in some areas of case 1, to 30% in other areas of case 4. The number of GFAP-positive cells detected in four of the five tumors was minimal. In the remaining tumor, 10% to 14% the positively GFAP antisera-stained cells could be seen in some areas; this tumor was considered a pineocytoma with astrocytic differentiation. MBP immunoreactivity was found in isolated cells only in one tumor. Neurofilaments or vimentin expression could not be found in tumoral cells. Synaptophysin was studied in two tumors (cases 4 and 5). Both tumors showed a fine granular neuropil pattern of immunoreactivity, but only in isolated cells of case 5, occasional cytoplasmic positivity could be determined. Based upon our results we can conclude that NSE and synaptophysin are markers that may be applied in the diagnosis of pineocytomas. Further, our results support the hypothesis that the tumoral cells in these neoplasms are of neuroendocrine origin.