Human effector cells of natural killer (NK) activity have been augmented by pretreatment with a partially purified preparation of interferon (IFN-beta). Using the 4-hr 51Cr release assay to measure cytotoxicity, the boosted effector cells, as well as the spontaneous NK cells, were nonphagocytic cells with receptors for the Fc portion of IgG. Augmentation of cytolytic activity occurred: (1) in medium with either fetal calf serum and human serum; (2) in the presence of absence of monocytes; (3) in both sheep RBC rosette-forming and non-rosette-forming populations; and (4) when only the effector cells were pretreated with interferon. This last observation led to the finding that less than or equal to 5 min of contact at 37 degrees C, 22 degrees C, or 4 degrees C with interferon was necessary for augmentation of cytotoxicity. Augmentation kinetics demonstrated significant boosting of NK activity in peripheral blood leukocytes and highly NK-enriched Percoll fractions after 1 hr of contact with IFN-beta or pure IFN-alpha-Collectively, these results indicate that NK boosting with interferon: (1) occurs after a rapid temperature-independent binding to the effector cells; and (2) has a rapid effect on the cytolytic process.