The influence of chicken leukocyte interferon (IFN) on the antibody-dependent cellular cytotoxicity (ADCC) of peripheral blood mononuclear cells of chickens has been investigated in vivo and in vitro. The cytotoxic effect was studied on sheep red blood cells (SRBC) coated with chicken anti-SRBC serum. Cytotoxicity was estimated using a 51Cr release assay system. A single intravenous injection of crude IFN led to an enhanced ADCC 6 to 12 h after the IFN injection, whereas by 24 h the activity had decreased. The ability of IFN to augment the cytotoxicity was not lost after phagocytic cell depletion. In vitro, the ADCC was boosted within 1-18 h by IFN, in a dose-dependent manner. We assume that the augmenting agent in vitro is IFN itself, as purified IFN had a similar activity, but mock IFN and trypsin-treated IFN showed no enhancing effect.