Immunoglobulin gene rearrangements in patients treated with BMT have restricted repertoire diversity. Clonal variability remains low for 3 months and reconstitution of the humoral immune system appears to follow a wave-like pattern. In the present study we analysed serum IgM and IgG repertoires in 44 patients from 1 week to 3 years after transplantation. We applied a quantitative immunoblot technique in combination with a newly developed method for estimation of repertoire diversity in complex mixtures of antibodies. Our results demonstrate that 60% of BMT patients have severely reduced diversity in the IgM repertoire during and after the first year post-BMT, compared with healthy controls. In contrast, the majority of patients have a polyclonal IgG repertoire, similar to that of healthy controls. Serum IgM repertoires remain oligoclonal even though the serum concentration of total IgM is within normal range around 6 months post-BMT. During the first years after transplantation IgM as well as IgG repertoires are less diverse in patients receiving a BM graft from a sibling donor compared with those receiving a graft from an HLA-matched unrelated donor. Patients in the latter group show a higher incidence of infections and minor antigen mismatches which may promote the development of a diverse immunoglobulin repertoire post-BMT.