We established a plasma cell line, NCI-H929, from a malignant effusion obtained from a patient with IgAK myeloma. The cell line was cultured in ACL-3, a defined serum-free medium, and was mycoplasma free. The cultured cells had the morphologic, ultrastructural and cytochemical features of plasma cells. They synthesized and secreted very high concentrations of IgAK. The tumor and cultured cells lacked Epstein-Barr virus nuclear antigen and most B cell antigens, but expressed the plasma cell associated antigen PCA-1. These studies demonstrate that NCI-H929 is a fully differentiated, highly secretory plasma cell line. While a modest number of human 'plasmacytoid' cell lines have been established, most are lympho blastoid lines lacking plasma cell features, while others appear to be less differentiated secretory cells. Most of NCI-H929 cells were near tetraploid, with six copies of chromosome 8 having an 8q + abnormality. Of major interest, the tumor and cultured cells had a rearrangement of the cellular c-myc proto-oncogene (located at 8q24) and expressed c-myc RNA. These studies link for the first time, at the molecular level, plasma cell tumors of two mammalian species, man and mouse. At present, we are investigating the precise nature of the DNA rearrangement in NCI-H929 cells and its relationship to the 8q+ abnormality by molecular cloning. We are drug marking the line for future use as a fusion partner for the generation of human monoclonal antibodies.