Cells derived from retinoblastomas grow slowly in vitro and only very rarely form tumors in nude mice. Matrigel, a mixture of components normally found in basement membranes, promotes the growth of Y-79 and WERI-Rb1 retinoblastoma (Rb) cells when added to suspension cultures of the 2 Rb cell lines. It also substantially increases cell adhesion in vitro. Y-79 cells, seeded into a Matrigel matrix, form round colonies over a 3-week period similar to those of control, weakly metastatic murine melanoma cells. In vivo, s.c. co-injection of Matrigel with either Y-79 or WERI-Rb 1 cells into nude mice promotes retinoblastoma tumor formation. Transplantation of as few as 1,000 cells allows for xenografting under these conditions, while no tumors were observed in the absence of Matrigel, even at 10 x 10(6) cells/inoculum. The tumors produced have the expected morphology and express an mRNA for a highly specific retina/retinoblastoma marker protein, the interphotoreceptor retinoid-binding protein. Thus, the xenografts obtained maintain the original morphological and molecular characteristics of the injected cells and represent a useful model for in vivo studies of retinoblastoma growth and treatment.