The development of new generation vaccines has focused on the use of natural immunologic adjuvants that are capable of enhancing a protective immune response, The use of cytokines as immunomodulators in livestock animals, particularly poultry, is becoming more feasible with the recent cloning of several cytokine genes and the progression of new delivery technologies, such as live vectors and DNA delivery, Given that chickens are reared under intensive conditions that are conducive to infection by opportunistic pathogens, the primary mechanism for disease control in poultry is early and effective vaccination, However, many poultry vaccines offer only short-term protection or give nonuniform responses within flocks. We have developed a model system with which to measure the adjuvant potential of cytokines in chickens. This involves measuring antibody levels following coadministration of chicken interferon-gamma (Ch-IFN-gamma) with sheep red blood cells (SRBC), Groups of SPF and commercial broiler birds were injected with two different doses of SRBC with and without coadministration of Ch-IFN-gamma. Three weeks later, all birds were boosted with SRBC alone. Sera were collected weekly and anti-SRBC antibody titers (total Ig and IgG) were determined by hemagglutination, Priming Ch-IFN-gamma resulted in enhanced primary and secondary (IgG) antibody responses that persisted at higher levels when compared with birds that received SRBC alone. Second, coadministration of Ch-IFN-gamma allowed a 10-fold lower dose of antigen to be as effective as a high dose of antigen that was given without Ch-IFN-gamma, Third, treatment with Ch-IFN-gamma resulted in an increase in the proportion of birds responding to antigen challenge, These results suggest the potential use for Ch-IFN-gamma as a vaccine adjuvant.