Three classes of human interferons (IFNs) have been defined on the basis of their immunological properties: the ‘Le’ or ‘α’ IFN, mainly derived from leukocyte or lymphoblastoid cells; the ‘F’ or ‘β’ IFN, mainly derived from fibroblast cultures; and the‘T’, ‘immune’ or ‘γ’ IFN, mainly derived from mitogen- or antigen-stimulated lymphoid cells¹. Whereas several individual species of Le IFN have been purified to homogeneity^2–4, it is generally considered that F IFN represents a single protein^5,6. Thus current efforts to clone human fibroblast IFN mRNA sequences are based on the observation that F IFN mRNA sediments in sucrose gradients as a single RNA species of size corresponding to 12–14 S (refs 7–10). We show here, using gel electrophoresis of mRNA, that two populations of translationally active human fibroblast IFN mRNA molecules exist—an abundant ‘14 S’ species and a scarce ‘11 S’ species. Microinjection of either species of mRNA into Xenopus oocytes leads to the synthesis of biologically active F-type human IFN. These data agree with and complement recent RNA hybridization studies of Weissenbach et al.¹⁰.