We investigated for rearrangements of the immunoglobulin (Ig) heavy and light chain genes and of the T cell receptor (TCRT) and (TCr) genes 45 biopsy samples from a variety of lymphoproliferative disorders. They were diagnosed histopathologically and immunophenotypically as non-Hodgkin''s lymphomas (NHLs) of the B cell type (19 cases), NHLs of the T cell type (3 cases), NHLs of undetermined cell type (3 cases), atypical lymphoid proliferation (1 case) and AIDS-related lymphadenopathies with florid polyclonal follicular hyperplasia (19 cases). A monoclonal proliferation of B cells was shown by DNA analysis in all 19 B cell NHLs. In two immunohistologically determined T cell NHLs (both diagnosed as mycosis fungoides) the cells had rearrangements of TCr gene, whereas in the third case (lymphoblastic NHL) the cells had rearrangements of Ig heavy chain and TCr and TCr genes. None of the B cell NHLs exhibited TCrand TCr gene rearrangement bands. All the undetermined cell NHLs demonstrated rearrangements of Ig heavy chain gene associated with the germ line TCrand TCr genes; in two cases light chain gene rearrangements were also found. The atypical lymphoid proliferation, in which the differential diagnosis was between a reactive or malignant process, and two out of 19 cases of florid polyclonal follicular hyperplasia showed a clonal B cell population by DNA analysis. This study indicates that there was a strong correlation between the rearrangements of specific genes and the immunophenotype of the NHL; moreover, DNA analysis of tissue biopsy specimens from phenotypically undetermined cell NHLs and from equivocal lymphoid proliferation using Ig and TCR gene probes yelded an answer in the cases analyzed. The significance of clonal B cell expansions found in two AIDS-related lymphadenopathies should be interpreted with caution.