Deregulated c-myc expression, as a consequence of translocation of the c-myc gene to one of the immunoglobulin loci, appears to play an important role in the pathogenesis of several B-cell tumors, including Burkitt's lymphoma, mouse plasmacytoma and rat immunocytoma. This study investigated the expression of c-myc and 2 other members of the myc gene family, L- and N-myc, at the mRNA and protein level, and analyzed for possible rearrangements of these genes in the human counterpart to the mouse plasmacytoma--multiple myeloma (MM). Nine well-characterized MM cell lines were examined by using Northern- and Southern-blot analysis and immunoprecipitation. The c-myc gene was found to be highly expressed in most MM cell lines. The level of expression was comparable to that observed in the COLO 320 and HL-60 cell lines, carrying amplified c-myc genes, and to that of B-cell lines with a higher proliferative activity than the MM cell lines. In the U-266 MM cell line, L-myc, but no c-myc mRNA or protein, was found. The L-myc gene was expressed in both early- and late-passage U-266 cells, suggesting that the L-myc expression was not the result of the in vitro cultivation. N-myc was not expressed in any of the MM cell lines. No rearrangements of c-myc or L-myc genes were found. We thus conclude that (a) in contrast to the corresponding mouse and rat B-cell tumors, c-myc is not frequently rearranged in MM; (b) c-myc is highly expressed in most MM lines; and (c) L-myc but not c-myc is expressed in the U-266 MM cell line.