The literature on immunosenescence has focused mainly on T cell impairment.With the aim of gaining insight into B cell immunosenescence, we investigated the serum immunoglobulin levels in a cohort of 166 subjects (20-106 years). Serum IgG (and IgG subclasses) were quantified by the nephelometric technique, IgE by CAP system fluorescence enzyme immunoassay, and IgD by radial immunodiffusion (RID). There was an age-related increase of IgG and IgA; the IgG age-related increase was significant only in men, but IgG1 levels showed an age-related increase both in men and women, whereas IgG3 showed an age-related increase only in men. IgE levels remain unchanged, whereas IgD and IgM serum levels decreased with age; the IgM age-related decrease was significant only in women, likely due to the relatively small sample of aged men. Thus, in the elderly the B cell repertoire available to respond to newantigenic challenge is decreased.Alot of memory IgDB cells are filling immunological space and the amount of naïve IgD+B cells is dramatically decreased. This shift away from a population of predominantly naïve B cells obviously reflects the influences of cumulative exposure to foreign pathogens over time. These age-dependentBcell changes indicate that advanced age is a condition characterized by lack of clonotypic immune response to new extracellular pathogens. In any event, the increase of memory B cells and the loss of naïve B cells, as measured by serum IgD levels, could represent hallmarks of immunosenescence and could provide useful biomarkers possibly related to the life span of humans.