AbstractWe investigated thein vivodifferentiation potential of Y79 human retinoblastoma cells following pre-treatment with two novel neurotrophic agents: PEDF (human recombinant pigmented-epithelial derived factor) or IPM (interphotoreceptor matrix) wash. These agents were able to induce a significant degree of morphological differentiationin vitro. However, 48 days after subretinal transplantation of pre-treated cells, massive tumor formation was apparent. In contrast, Y79 cells pre-treated with retinoic acid/sodium butyrate, which attain a lesser degree of morphological differentiation, did not produce tumors over a 30 to 60 day-survival time (del Cerro et al.,Brain Research, 12–22, 1992). We conclude that for PEDF and IPM, the degree ofin vitrodifferentiation and the degree of mitotic arrest are independent features.