A panel of established cell lines and many primary cell specimens from lymphomas and leukemias as well as from normal lymphatic tissues were tested for tumorigenicity by intracranial heterotransplantation in nude mice. Not only lymphoma and leukemia cell lines, but also lymphoblastoid cell lines, lacking markers of malignancy, were tumorigenic in the brains of nude mice. These findings indicate that tumorigenicity following intracranial heterotransplantation in nude mice cannot be used as proof for the malignant nature of established cell lines. Heterotraplantation of primary cell specimens yielded only a few tumor takes. When primary cells were infected with exogenous Epstein-Barr virus prior to the transplantation procedure, tumorigenicity could be significantly increased. Cytogenetic evaluation of tumors growing after intracranial transplantation of human hematopoietic cells showed, in some cases, a selection of cytogenetically aberrant cell clones.