Asymptomatic forms of monoclonal gammopathies (MG) are recognized with increasing frequency; their recognition and differentiation from the symptomatic forms of MG appear imperative, since the therapeutic approaches are different. Available clinical and laboratory indexes lack specificity required for useful and practical discrimination; presently, we must still rely on the timecourse monitoring of such laboratory values as hemoglobin levels, M-protein concentrations, and presence of Bence Jones proteins. Elucidation of histocompatibility A and W antigenic profiles, as well as the functions and kinetics of B-lymphocytes from such patients, appear most promising. Evidence of the causative role of extrinsic and intrinsic antigenic stimulation in MG production is increasing; segregation into two distinct concentration ranges of M-proteins in the asymptomatic and symptomatic groups suggests two control levels of the expression of immune response (Ir) genes, due to partial or complete derepression of the latent Ir gene functions, reflecting "partial" (asymptomatic, benign MG) and "complete" (symptomatic, malignant MG) monoclonal immune responders.