Cloned L cells were shown to be very heterogeneous in their time and dose-responses to mouse interferon. Sensitive cells transferred interferon-induced viral resistance to less sensitive cells making them equally sensitive. A small fraction of cells was found to determine the overall response of the “parental” L-cell population. Based on these findings a new mechanism of interferon action on cells not in contact with interferon was proposed. The implications of this proposal to polypeptide hormone action are discussed. © 1979, SAGE Publications. All rights reserved.