Oviduct-specific expression of heterologous recombinant proteins in transgenic birds is a promising technology for the large-scale production of therapeutic proteins in eggs. We describe the production of recombinant human interleukin 1 receptor antagonist (rhIL1RN) in the eggs of transgenic quails. To drive tissue-specific expression of rhIL1RN, a 1.35-kb fragment of the chicken ovalbumin promoter, which contains both the steroid-dependent regulatory element and the negative regulatory element, was used. A transgenic quail was generated by microinjection of a concentrated stock of lentivirus into stage X blastodermal cells. A single copy of the transgene was integrated into the seventh intron of the gene for conserved oligomeric golgi complex protein 5 (COG5) on chromosome 1. As expected, rhIL1RN expression was restricted to oviductal tissue, and the amount of protein deposited in the eggs of homozygous transgenic quails ranged from 88.7 to 233.8 ng/ml. Transgene expression was conserved from the G(1) generation to the G(4) generation, and there was no evidence of transgene silencing. In a bioassay using the EL4.NOB-1/CTLL-2 coculture system, no significant difference was observed between the egg-produced rhIL1RN and a commercially available rhIL1RN (anakinra).