Genes for interferon-tau (IFNT) have been cloned from several Bovidae, and the IFNT lineage has been predicted to have arisen from the IFNW, as the divergence of the Ruminantia from other artiodactyls. Southern genomic blotting with probes specific for IFNT identified a gene in the giraffe, a nonbovid member of the Ruminantia. Here this gene has been cloned, sequenced, and expressed. It encodes a 172-amino acid mature protein with antiviral activity on bovine cells. Giraffe IFN-tau lacks the normally conserved Cys99 but has a pair of other cysteines (Cys64 and Cys86) that could provide a disulfide bridge. The giraffe IFNT gene possesses the highly conserved promoter region that distinguishes IFNT from IFNW. It seems likely that IFNT emerged before the divergence of the Giraffidae and Bovidae, which occurred some 24 million years ago.