Technical Abstract: Marek’s disease virus (MDV) encodes a basic leucine zipper oncoprotein, meq, which structurally resembles jun/fos family of transcriptional activators. It has been clearly demonstrated that deletion of meq results in loss of transformation and oncogenic capacity of MDV. The rMd5'meq virus provided superior protection than CVI988/Rispens vaccine in 15 x 7 chickens when challenged with a very virulent plus (vv+) strain of MDV, 648A. The rMd5'meq construct was also shown to be an effective vaccine in commercial chickens that were challenged under field conditions by exposure to seeder chickens inoculated with MDV strain 686, a vv+ and arguably the most pathogenic strain of MDV. Although deletion of meq gene renders the virus non-oncogenic, it still induces lymphoid organ atrophy like that of the parental rMd5, in highly susceptible MDV maternal antibody negative (MAb-) chickens. We have generated 50 cell culture passages of attenuated rMd5'meq viruses and found no significant lymphoid organ atrophy beginning at 40th passage onward when compared with normal control chickens. The protective ability of these attenuated meq null viruses against challenge with vv+ MDV, strain 686 is similar to the original virus at 19th passage but equal to or better than CVI988/Rispens in maternal antibody negative chickens. The data indicates that attenuation of these meq null viruses has no influence on their protective efficacy, but eliminated lymphoid organ atrophy and rendered them safe to use even in MAb- chickens, a characteristic that should facilitate commercialization and licensing by vaccine manufacturers.