The karyotypes of pristane-induced mouse plasmacytomas were studied by G banding. Only primary tumors or early passage generations were analyzed. In contrast to murine T cell leukemias that showed a regular trisomy of chromosome 15, all plasmacytomas showed a consistent translocation of the distal part of chromosome 15 to either chromosome 6 [rcpT(6; 15)] or 12 [T(12; 15)]. The specific breakpoints were at 6C, 15D3/E or D2/3 and 12F2. Early passage generations often showed a mixed population with two different translocations, suggesting polyclonal origin. Considered together with the known karyotypic features of murine and human lymphomas, these findings support the theory that the nonrandom chromosomal changes in lymphoproliferative malignancies are associated with the type of the target cell, rather than with the etiological agent. Moreover, the involvement of the chromosomes known to carry the heavy chain (12) and the light chain (6) determinants, respectively, raises the question of whether the translocations may be related to the DNA level rearrangements known to occur during the differentiation of normal plasma cells.