We have studied the effect of two species of recombinant alpha interferon (IFN) on peripheral blood NK cell cytotoxicity of normal donors against K-562 target cell line. Both recombinant IFNs, species A (IFN-alpha rA) and species D (IFN-alpha rD) significantly augmented, in a dose-dependent manner, NK cell cytotoxic potential. Highest augmentation was achieved with doses in the range of 10(3)-10(4) u/ml. Augmentation was observed independently whether the IFN-alpha r was added directly to the cultures of the tumor and effector cells, or whether the effector cells were preincubated with IFN-alpha r. Increase in cytotoxicity was evident within 10 min of incubation with IFN-alpha rA and was further potentiated with increasing incubation time. In general, no synergistic effect of IFN-alpha rA and IFN-alpha rD was observed when both of these species were added together to target and effector cells. Studies on the mechanism of IFN-alpha r action demonstrated that neither species of IFN-alpha r affected NK cell tumor-binding potential, but augmented cytotoxic-tumor binding potential and maximum rate of lysis. NK cell recycling capacity of most of the donors was augmented by IFN-alpha rA. These data illustrate that pure preparations of IFN-alpha rA and IFN-alpha rD augmented NK cell antitumor potential in vitro, suggesting that these agents may have therapeutic potential in neoplasias when their mechanism of action is more understood, and optimal conditions for treatment are developed.