Advances in immunology and oncology provide the basis for a unifying view of the diverse human neoplastic disorders arising from cells of the B-cell series of immunocytes. As is reflected by their immunoglobulin product (whether cell bound or secreted), such neoplasms are almost always monoclonal. A hypothesis is reported which relates the various clinical syndromes to the normal pathway of B-cell differentiation This approach permits appreciatior of the inter-relation of chronic lymphocytic leukæmia, the various lymphomas, plasma-cell tumours, and rarer variants. Many clinical mani festations and para-neoplastic syn dromes of B-cell neoplasia can now also be related to the specific anti-body, secreted immunoglobulin, and/ or non-immunoglobulin products of the tumour cells. Observations on the natural history of both experimental and clinical myelomatosis, as well as detailed studies of the kinetics of the proliferation of myeloma cells in man, have led to a " two-hit " hypothesis of the evolution of myeloma. In this scheme, the first hit is a " triggering " by specific antigen, leading to a required monoclonal expansion, while the second hit is the oncogenic event. Some benign monoclonal gammopathies seem to be examples of an unusually exuberant response to the first hit, whereas others seem to be "minimal-deviation "malignancies after the second hit.