In an attempt to establish an in vivo animal model to study Hodgkin's disease (HD) and the histogenesis of the neoplastic cell of the disease - the Reed-Sternberg (RS) cell, and to study non-Hodgkin's lymphomas (NHL), severe combined immunodeficient (SCID) mice were transplanted with fresh biopsy material from 17 cases of HD and 25 cases of NHL. Five of the Hodgkin's (3 lymphocyte predominant, 1 nodular sclerosing and 1 mixed cellularity) and 7 of the non-Hodgkin's lymphomas (3 centroblastic, 1 immunoblastic, 1 follicular lymphoma and 2 biopsies from a case of B cell large cell anaplastic lymphoma) produced human high grade B cell lymphomas in the mice. All of the Hodgkin's disease derived SCID tumours expressed the Epstein-Barr virus (EBV) gene products EBER, EBNA-2 and LMP-1, even though only 1 of the original biopsies showed EBV positive RS cells. However, EBV clonality analysis showed that the EBV positive clone present in the original biopsy was not present in the SCID tumour. Morphologically, these tumours resembled polymorphous immunoblastic lymphomas, although in each case there were a few RS-like cells. The HD-derived SCID tumours did not retain the phenotype of the original biopsies, instead exhibiting an activated B cell phenotype with high expression of the CD23 and CD43 antigens. All HD-derived SCID tumours showed clonal Ig gene rearrangements. Further characterisation demonstrated that all of the HD-derived SCID tumours showed Ig secretion and contained the normal diploid DNA content.