Southern blotting was used to detect rearrangement of the bcl-2 gene in 104 cases of non-Hodgkin's lymphoma subclassified by the Working Formulation, 24 cases of B cell chronic lymphocytic leukemia (B-CLL) and 14 cases of T cell malignancy. Earlier workers reported rearrangement of this gene (located on chromosome 18) in a major fraction of follicular lymphomas, lymphomas in which a 14;18 chromosome translocation is frequently observed. In the present study, bcl-2 was rearranged in 30% (11 of 37) of follicular lymphomas and 19% (11 of 58) of diffuse lymphomas of follicle center cell lineage. In 18 of 19 samples studied, the rearranged bcl-2 fragment also hybridized with a probe for the joining region of the immunoglobulin heavy chain gene located on chromosome 14, indicating a 14;18 translocation. In lymphomas not derived from follicle center cells, ie, diffuse lymphomas of small B lymphocytes, B-CLL and T cell neoplasms, the bcl-2 gene was always in germline configuration. The frequent rearrangement of bcl-2 in a variety of B cell lymphomas of diffuse morphology (small cleaved cell, large cell, small noncleaved cell and immunoblastic) is noteworthy.