Natural killer (NK) activity was assayed in fresh peripheral blood mononuclear cells (PBMs) from cancer patients receiving interferon (IFN)-beta ser. Patients received a single intravenous injection of IFN-beta ser (90 x 10(6) IU m-2) on alternate days for 2 weeks, followed by a higher dose (180 x 10(6) IU m-2) on the same schedule. PBM NK lysis of K562 target cells was significantly increased in PBMs sampled 24 h after the initial injection (P < 0.05). At the end of the first 2 weeks of the protocol, NK cytotoxic activity of PBMs had fallen below the original baseline levels; the higher IFN dose subsequently given was without effect. However, significant increases in the proportion of CD16+ cells were seen following each injection. A positive correlation was also seen between the increased lytic activity of CD16+ NK cells and the proportion of CD38+ NK cells, but not the proportion of CD56+ NK cells. In vitro IFN-treatment of these in vivo-treated PBMs resulted in a further increase in NK activity. Pre-exposure in vivo to IFN-beta ser seems to prime the PBMs to respond to in vitro stimulation by IFN-gamma, which otherwise had no effect. Phenotypic analysis of PBMs after in vitro exposure to IFN-beta ser showed that the levels of CD16+, CD38+ and CD56+ cells did not change. All the NK activity responding to IFN-beta ser was found in the CD16+ enriched population of PBM, suggesting that it is unlikely that in vivo redistribution of CD16+ subsets representative of NK cells has occurred in the peripheral blood.