The histogenesis of retinoblastoma, the most common intraocular neoplasm of childhood, remains controversial. Previous studies have attributed the origin of the tumour to neuronal, glial or primitive stem cells of retina. In the study described here we have used immunofluorescence to search for the presence of a neuronal marker, neurone-specific enolase (NSE) and a glial marker, glial fibrillary acidic protein (GFAP), in the cells of the human retinoblastoma line Y-79 (ref. 4), before and after successful differentiation into neuronal and glial-like cells. We found that all undifferentiated cells contain both NSE and GFAP, whereas the differentiating neuronal and glial-like cells gradually lose one marker and selectively express the marker that correlates with their morphology. Our results support the notion that retinoblastoma originates from a primitive bipotential (or multipotential) neuroectodermal cell.