Waldenström's macroglobulinemia (WM) represents an indolent incurable human B-cell tumor. We have successfully established a permanent cell line, WSU-WM, without growth factors or viral transformation, from the pleural effusion of a 60-year-old man with IgM kappa WM. Phenotypic characterization of WSU-WM shows IgM lambda and expression of other B-cell markers. Karyotypic analysis shows a male chromosome complement with several clonal aberrations, including t(8;14)(q24;q32). Molecular characterization shows deletion of kappa and rearrangement of lambda light chain genes indicating a class switching. Both the secretory (s mu) and membrane (m mu) components of IgM are expressed. In addition, the breakpoint on 8q24 is downstream of exon 3 of the c-myc oncogene. WSU-WM grows in liquid culture and soft agar. When cells were injected subcutaneously in immune deficient mice, six of seven SCID mice developed subcutaneous tumors as opposed to three of seven in the athymic nude mice. When a WSU-WM SCID tumor was passaged in vivo in the SCID mice, the take rate was 100%. This xenograft model and a soft agar disk-diffusion assay were used to test the efficacy of standard chemotherapy agents against this tumor in vivo and in vitro, respectively. The cell line and the assays described herein can be used as a model to facilitate the discovery of new therapeutic agents or modalities for this disease.