CMV induces the expansion of a unique subset of human NK cells expressing high levels of the activating CD94-NKG2C receptor that persist after control of the infection. We investigated whether this subset is CMV specific or is also responsive to acute infection with EBV. We describe a longitudinal study of CMV2 and CMV+ students who were acutely infected with EBV. The NKG2Chi NK subset was not expanded by EBV infection. However, EBV infection caused a decrease in the absolute number of immature CD56bright CD162 NK cells in the blood and, in CMV+ individuals, induced an increased frequency of mature CD56dim NKG2A+CD57+ NK cells in the blood that persisted into latency. These results provide further evidence that NKG2C+ NK cells are CMV specific and suggest that EBV infection alters the repertoire of NK cells in the blood.