This thesis comprises a series of studies conducted to elucidate host responses to Marek's disease virus (MDV) in two body compartments; spleen which is a major secondary lymphoid organ involved in elicitation of immune response and feathers, which are the site of virus shedding in MDV-infected chickens. To establish a reliable method for quantification of MDV genome, a real-time PCR technique was developed. Overall, this PCR technique was proven to be reproducible and to have a low inter- and intra-assay variation. The technique was then validated quantifying viral genome load in feathers of chickens infected experimentally with MDV. This technique was used in subsequent studies presented in this thesis for quantification of MDV as well as related vaccine strains in feathers and spleen. In a study aimed at identifying immunological mediators that are involved in immunity conferred by Marek's disease (MD) vaccines, it was demonstrated that lower expression of cytokine genes such as interleukin (IL)-6, IL-10 and IL-18 in spleen was associated with protection in vaccinated chickens. Further, the study indicated that although vaccines can confer protection against disease and reduce MDV load in some tissues such as spleen, they are not able to reduce virus replication and shedding from feathers. Considering the importance of feathers in MDV shedding, two separate experiments were conducted. In the first study, in response to MDV, significant increase in viral genome load and transcripts were associated with an increase in the expression of major histocompatibility complex (MHC) class I gene, cytokine genes such as IL-6, IL-10 and interferon (IFN-[gamma]) and the infiltration of CD4+ and CD8+ T cells. In the second study, both CVI988 and herpesvirus of turkeys (HVT) vaccine viruses replicated in feathers and stimulated local host responses, characterized by the expression of cytokine genes such as IFN-[gamma] and infiltration of CD8+ T cells. In conclusion, host responses are initiated in response to MDV infection and vaccination against MD both in spleen and feathers. There is a difference in elicited host responses in these body compartments; in spleen it is effective in curtailing MDV replication, whereas in feathers host responses are associated with the persistence of MDV.