Fourteen Non-Hodgkin's lymphoma cell lines were generated and assessed for the presence of structural p53, c-myc and bcl-2 gene changes. Single or multiple changes were observed in 11 of the lines. Alterations of the p53 gene were most frequent and documented for 10 lines by immunoprecipitation using the antibodies PAb 240 and PAb 1801, sequencing studies and Southern blot analysis. A detailed study was performed in one of the cell lines (OCI-Ly 4) for which material of the original tumor sample was available. Two point mutations identified by sequencing cDNA derived from the cell line were also present in the original tumor specimen. In contrast, DNA prepared from fibroblasts of the same patient did not show the mutations. Six of the 14 lines demonstrated c-myc rearrangements, while bcl-2 changes were observed in 4. The presence of c-myc was associated with shorter survival of this group of patients with aggressive disease. None of the other changes present as single or composite alterations were correlated with clinical outcome measures.