The monoclonal gammopathies are a group of disorders characterized by proliferation of a single clone of plasma cells that produce a homogeneous, monoclonal (M) protein. The structure of immunoglobulins, relationship of normal (polyclonal) immunoglobulins to myeloma and macroglobulin (monoclonal) immunoglobulins, pattern of monoclonal immunoglobulin overproduction, and laboratory methods for the recognition and study of monoclonal proteins in the serum and urine are reviewed. Interpretation of these laboratory tests is emphasized. The demonstration of a monoclonal protein in the serum or urine of a patient suggests multiple myeloma or one of its variants (solitary plasmacytoma of bone, extramedullary plasmacytoma, or plasma cell leukemia); Waldenström's macroglobulinemia or, occasionally, lymphoma; heavy-chain diseases (gamma, alpha, and mu); primary amyloidosis; and monoclonal gammopathies of undertermined significance. The electrophoretic and immunoelectrophoretic patterns found in the monoclonal gammopathies are discussed. Periodic electrophoresis of the serum and urine is essential in the follow-up and management of patients with a monoclonal gammopathy.