The present invention provides biologically active variants of human α-2b-interferon. The variants contain carboxy terminus truncations when compared with the amino acid sequence of full-length human α-2b-interferon. It is the novel finding of the present invention that these truncated variants have the biological activity of full-length human α-2b-interferon. The invention encompasses these biologically active variant α-interferons, as well as polynucleotides encoding these interferons. Expression cassettes comprising these polynucleotides and host cells comprising the expression cassettes are also provided. The invention also provides compositions comprising variant α-interferon polypeptides and a pharmaceutically acceptable carrier.