Dose-response curves of interferons in different sensitive cells are regularly sigmoidal. In somatic monkey-mouse hybrid cells, however, a significant decrease in the slope of the curve for primate interferon was observed, while the dose-response effect was unaltered for mouse interferon. High concentrations of primate interferon were 10- to 100-times less effective in hybrid clones than in parental monkey CV-1 cells; at low concentrations the antiviral effect was 10- to 20-times higher in hybrid clones than in the parental cells. The receptor(s) for primate interferon located on the cell membrane was destroyed by trypsin but not by EDTA. Similarly, acid pH inactivated these receptor sites. We, thus, postulate that the antiviral effect is, at least partially, related to the amount of interferon taken up by the cells. Uptake could be conditioned by active cooperation of two cell-specific factors: a receptor and an activator. The activator might be missing or inactivated for primate interferon in the hybrid cells. We suggest that the putative antiviral protein is not cell-species specific, and that information for its synthesis in the hybrid cells might be located on a mouse rather than a monkey chromosome.