Surgical specimens from 36 medulloblastomas (25 classic and 11 desmoplastic) were studied by peroxidase-antiperoxidase (PAP) immunohistochemistry with antibodies against the class III beta-tubulin isotype (beta-tubulin), synaptophysin, retinal S-antigen (S-Ag), and glial fibrillary acidic protein (GFAP). We found that neoplastic cells expressed beta-tubulin in 91% of the tumors (23 classic and 10 desmoplastic), synaptophysin in 75% (19 classic and 8 desmoplastic), S-Ag in 44% (11 classic and 5 desmoplastic), and GFAP in 11% of medulloblastomas (2 classic and 2 desmoplastic). Synaptophysin and beta-tubulin positivities were observed in undifferentiated neoplastic cells, in cells forming neuroblastic rosettes, and in pale islands, while S-Ag immunopositivity was noted in undifferentiated cells, occasionally in beta-tubulin-negative neuroblastic rosettes, and exceptionally in pale islands. Large pale islands, in two desmoplastic medulloblastomas, exhibited distinct patterns of immunoreactivity to the above markers, suggesting neuronal and glial differentiation in the central area, and intense neuritic development in the peripheral zone. Our findings confirm the predominant capacity of medulloblastoma cells to differentiate along neuronal cell lines and indicate that large pale islands, in desmoplastic medulloblastomas, represent well-organized areas for neuronal and, to a lesser degree, astroglial differentiation. Furthermore, it appears, in our cases, that immunohistochemical features do not represent clear-cut prognostic indicators in patients with medulloblastomas.