Circulating post-switch B cells have been proposed as proliferative and disseminating progenitors in multiple myeloma. It is unclear whether the class-switched antigen receptor expressed at the surface of these cells plays a role in their expansion. In this work, the signaling status of IgG B cell receptor (BCR) isolated from the lysates of peripheral blood lymphocytes of 32 patients with IgG multiple myeloma, at the time of diagnosis, was investigated by examining whether phosphorylation of BCR Igalpha and Igbeta signal transducer factors (co-receptors) or other signaling molecules was abnormal in these cells when compared with healthy controls. In IgG BCR of normal controls, weak phosphorylation of 56 and 61 kDa Src kinase-related proteins and unphosphorylated co-receptors were found. In myeloma, p56 and p61 kDa proteins, co-receptors, and other IgG BCR-associated proteins from the signal cascade were phosphorylated. Myeloma patients can be classified into subgroups by IgG BCR phosphorylation profiles which characteristically coordinated with the level of IgG paraprotein in serum and the stage of disease. There was a correlative trend between the extent of phosphorylation reduction and advanced stage of disease. Reduced phosphorylation was more pronounced with advanced stages of multiple myeloma.