Colibacillosis is considered one of the more costly diseases encountered in the production of market turkeys. It is responsible for a significant amount of mortality in birds between the ages of 6-12 weeks. Research conducted over the past 5 years has shown that within the Shenandoah Valley production area, multiple primary infectious agents are responsible for the predisposition of turkeys to colibacillosis. These agents were first identified as potential contributors through field case studies. They include hemorrhagic enteritis (HE) virus, Newcastle disease virus, and Bordetella avium. Further retrospective serologic studies affirmed the role of these primary agents and uncovered the potential involvement of Mycoplasma meleagridis. Trials were conducted to determine the reproducibility of some multiple agent interactions under laboratory conditions. It was found that Newcastle disease virus or B. avium infection followed by HE virus and Escherichia coli challenge produced clinical colibacillosis. It is believed that hemorrhagic enteritis virus is the pivotal agent in this process of predisposition. Almost all turkeys are vaccinated for hemorrhagic enteritis in the field. The virulent strains of the virus are known to be immunosuppressive. It is suspected that the vaccine strains are mildly so. Infection with HE vaccine virus was shown to cause an increase in CT8+ cells in peripheral blood. These cells are believed to be suppressor T-cells and may account for the reputed immunosuppressive effects of the virus. Thus, interactions of multiple infectious agents including Newcastle disease virus, B. avium, M. meleagridis, and HE virus appear to be involved in the predisposition of turkeys to secondary E. coli infections. / Ph. D.