We have studied the effect of interferon in vivo (induced by polyinosinic-polycytidylic acid (pIC] on the natural killer (NK) cell lytic activity and on the numbers of large granular lymphocytes (LGL) and target-binding cells (TBC) in different lymphoid compartments. One day after the pIC induction the spleen contained two- to four-fold increased lytic activity without a significant change in percentages of TBC and LGL. In the peripheral blood the lytic activity was 12- to 40-fold higher, and a concomitant clear increase in the number of LGL and TBC was seen. In the lungs the increase in lytic activity was 8- to 16-fold and in the number of LGLs ca. 3-fold. These results demonstrate that not only the lytic activity of the pre-existing NK cells but also the total amount of NK cells is clearly elevated in the body, but this could be seen more significantly in other highly NK-active organs than the spleen.