The cytokine IL15 is required for survival and activation of natural killer (NK) cells as well as expansion of NK-cell populations. Here, we compare the effects of continuous IL15 infusions on NK-cell subpopulations in cancer patients. Infusions affected the CD56^bright NK-cell subpopulation in that the expansion rates exceeded those of CD56^dim NK-cell populations with a 350-fold increase in their total cell numbers compared with 20-fold expansion for the CD56^dim subset. CD56^bright NK cells responded with increased cytokine release to various stimuli, as expected given their immunoregulatory functions. Moreover, CD56^bright NK cells gained the ability to kill various target cells at levels that are typical for CD56^dim NK cells. Some increased cytotoxic activities were also observed for CD56^dim NK cells. IL15 infusions induced expression changes on the surface of both NK-cell subsets, resulting in a previously undescribed and similar phenotype. These data suggest that IL15 infusions expand and arm CD56^bright NK cells that alone or in combination with tumor-targeting antibodies may be useful in the treatment of cancer. Cancer Immunol Res; 5(10); 929–38. ©2017 AACR.