Nonrandom translocations with breakpoint at band q21 on chromosome 18 might cause bcl-2 gene deregulation and might contribute to neoplastic transformation in human lymphomas. As the pattern of expression of bcl-2 in hematopoietic cells is still unclear, we have measured the level of the corresponding messenger RNA (mRNA) in a variety of myeloid and lymphoid cell malignancies not usually associated with the t(14;18) translocation. Molecular genetic analysis showed that bcl-2 was rearranged in only 2 of 77 patients: one was affected by hairy cell leukemia and one by diffuse small cleaved cell lymphoma with peripheral blood invasion. Although in rare cases of myeloid leukemia fairly high levels can be found, the expression of bcl-2 appears to be typical of certain lymphoid malignancies. High levels of bcl-2 mRNA had been found, previously, in established pre-B-cell lines. However, in fresh specimens, the peak level of bcl-2 expression shifts to a more differentiated cell type, represented by the long-living B lymphocytes that are found in most cases of chronic lymphocytic leukemia. bcl-2 gene product might have a role in prolonging cell survival and, even in the absence of translocations, might contribute to some of the biologic features that are typical of this disorder.