A high incidence of oligoclonal serum M-components is observed in multiple myeloma (MM) patients treated with autologous stem cell transplantation (ASCT). To determine whether these M-components are produced by myeloma clonally related cells or caused by an aberrant B-cell regeneration we analysed by semi-nested ASO-RT-PCR and DNA sequencing the immunoglobulin (Ig) variable genes (VH) obtained from bone marrow samples obtained before and after transplantation and peripheral blood stem cell (PBSC) samples from seven patients. Myeloma clonally related cells are identifiable by the expression of variant Ig heavy chain isotypes and were detected in two patients at presentation. No myeloma clonally related cells were found in post-transplantation samples (n = 7) in spite of the appearance of new serum M-components. However, in two cases we amplified sequences from post-transplantation bone marrow cells that were able to bind to the B-cell clone-specific CDR3 oligonucleotides but showed no further similarity regarding the VDJ rearrangement. These data indicate that serum oligoclonality post-transplantation is not caused by myeloma clonally related B cells but rather by the regenerating B-cell compartment.