The frequency of monoclonal gammapathies (MG) and their possible origin were investigated in renal graft recipients undergoing immunosuppressive treatment. In a cross-sectional study, homogeneous immunoglobulins were found in 30% of the patients investigated. This incidence was 10-times higher than that in a control group of patients with chronic renal failure on dialysis treatment. The increase in the frequency of homogeneous immunoglobulins in the renal transplant recipients was related to the age of the patients but not to the duration of the immunosuppressive treatment. A longitudinal study in 55 patients demonstrated that most of the MG reflected transient B-cell monoclonal proliferations, probably due to an immunodeficiency; however, the incidence of benign and malignant B-cell neoplasias seemed also to be unusually high. These findings indicate that the immunosuppressive treatment enhances and accelerates an immunodeficiency which develops spontaneously with aging of the immune system; it also may contribute to the development of other age-related, both benign and malignant monoclonal B-cell proliferative disorders.