Analysis of IgH and TcR-gamma genes using consensus primers identifying junctional regions of rearranged genes by polymerase chain reaction (PCR) was performed on tissues involved by Hodgkin's disease (HD) in 90 cases and was correlated with the immunophenotype of Hodgkin and Reed-Sternberg (HRS) cells and the presence of Epstein-Barr virus (EBV) within these cells. Clonal IgH gene rearrangements were found in 1/5 cases of lymphocyte predominance (LP) subtype and none was positive for EBV. In 85 cases of classic HD, no IgH or TcR-gamma gene rearrangements were found in 51 (60 per cent) cases. A similar percentage, but not the same cases, were of null (non-B, non-T) phenotype. Of 30 cases where a B phenotype was assigned to HRS cells, nine had IgH gene rearrangements, three had TcR-gamma gene rearrangements, and two had both genes rearranged. None of the five cases assigned to T phenotype of HRS cells showed rearrangement of TcR-gamma genes, but two cases showed rearranged IgH genes. Among 41 cases of null phenotype, ten had IgH gene rearrangements, five had TcR-gamma gene rearrangements, and three cases had both genes rearranged. Whereas EBV was detectable in HRS cells in 17/43 classic HD cases of assigned B phenotype, EBV was also detectable in 2/5 cases of assigned T phenotype and in 21 cases with the null phenotype. Furthermore, there was no correlation of EBV with the presence or lack or IgH or TCR-gamma gene rearrangements. Of the remainder, half (30 per cent) expressed antigens associated with lymphocytes without an appropriate genotype. The results confirm lymphocyte-lineage committed cells at the origin of HRS cells in 40 per cent of cases. Any hypothesis of a non-lymphocytic origin of HRS cells will require the inducibility of CD30 on candidate precursors and the methodology for probing genetic events in such cells to be addressed.