It has been reported that infectious mononucleosis (IM)-symptomatic primary Epstein-Barr virus infection produces a global down-regulation of interleukin-15 receptor-alpha (IL-15Ralpha) on T cells and natural killer cells associated with a defective IL-15 responsiveness that lasts for many years after the disease episode. In contrast with these results, our data indicate that, in the T-cell compartment derived from remote IM subjects, there is no quantitative or qualitative defect in the expression of the IL-15Ralpha chain and no deficit in T-cell responsiveness to IL-15. We observed efficient signal transduction, survival, and proliferation even in response to low IL-15 concentrations. These data are relevant and shed new light on the immune long-term response in IM subjects because they contradict the hypothesis that defects in Epstein-Barr virus-host immune balance may be correlated with a long-lasting global deficit in T-cell responsiveness to IL-15.