Immunoglobulin heavy chain (IgH) gene rearrangements were amplified in transbronchial lung biopsy (TBLB) specimens taken from five patients with primary lymphoma of the lung in whom the diagnosis was established by surgical specimens. By histopathological analysis of TBLB specimens, only two of the five cases were diagnosed as lymphoma, the other three cases being classified as equivocal due mainly to low levels of cellular atypia and to artefactual distortion. All five TBLB specimens, as well as the subsequent surgical specimens, showed a sharp monoclonal band of IgH gene rearrangement on electrophoresis of polymerase chain reaction (PCR) products. By contrast, three surgical biopsy specimens from cases of lymphoid interstitial pneumonia (LIP) showed smear polyclonal bands. No clonal rearrangements were detected in six non-neoplastic controls, including five cases of chronic bronchitis and one of sarcoidosis. The PCR products of three of the lymphoma cases were sequenced from both TBLB and surgical specimens. In all three cases, there was dominant expression of a particular rearrangement, assumed to be tumour-derived. In each case, the major clones derived from the TBLB and the surgical specimen were identical. In both lymphoma and LIP cases, more frequent usages of JH4 and JH6 were evident. The diagnosis of lymphoma can be confirmed on TBLB specimens by use of this technique.