A recombinant human hybrid alpha interferon (rIFN-alpha A/D) with antiviral, immunomodulating and cell-growth-inhibitory activity on murine cells strongly inhibited the development of experimental pulmonary metastases of the Colo 26 adenocarcinoma in BALB/c mice. Twenty-one days after i.v. injection of 5 X 10(4) cells, 8/8 control mice had greater than 200 lung tumour nodules whereas 1/6 mice receiving 500 ng rIFN-alpha A/D had one lung tumour nodule and the other 5 mice were tumour-free. Equally strong inhibition was seen in immunodeficient BALB/c nu/nu (athymic) and beige nu/nu (athymic and NK-deficient) mice. Scheduling experiments in vivo showed that the most important time of IFN treatment was from the day of tumour cell injection to day 5, although statistically significant reductions in lung tumour nodule number and lung weight were seen even when IFN treatment was started 7 days after cell injection. rIFN-alpha A/D was cytostatic to Colo 26 in vitro, causing 50% or more inhibition of cell growth or colony number at IFN levels that could be achieved in the sera of IFN-treated mice. Although rIFN-alpha A/D stimulated NK-cell activity in BALB/c mice, Colo 26 cells were resistant in vitro to such cells whether from control or IFN treated mice.