The influence of recombinant human alpha 2-interferon (alpha 2-IFN) therapy on various aspects of the immune system was studied in 18 patients with disseminated colorectal cancer. The IFN was given as continuous (20 × 106 units/m2 three times weekly) or intermittent (50 × 106 units/m2 daily for 5 consecutive days every 4 weeks) treatment. Natural killer (NK) cell activity increased during continuous treatment and in the patients receiving repeated cycles of IFN, all cycles seemed to be associated with an elevation of NK activity. Prior to treatment, addition of IFN to the assay in vitro induced an enhancement of NK activity, whereas during treatment, IFN in vitro did not cause any further enhancement of NK activity. The proportions of total T cells, suppressor T cells and helper T cells, as measured by Leu 1, Leu 2a and Leu 3a monoclonal antibodies, were not altered to any major extent during treatment. This was found to be the case also for the number of cells detected by monoclonal antibodies against NK cells (Leu 7). The phagocytic activity of granulocytes was not altered during IFN therapy, whereas the capacity of these cells to reduce nitroblue tetrazolium (NBT) increased after the first injection of IFN. The in vivo influence of high doses of highly purified recombinant alpha 2-IFN on NK cells and granulocytes seems to be similar to that of partially purified natural IFN-alpha.