Technical Abstract: We have previously shown that deletion of Meq gene from the genome of Cosmid-cloned rMd5 strain of Marek’s disease virus resulted in loss of transformation and oncogenic capacity of the virus. The rMd5 delta-Meq (Meq null) virus has been shown to be an excellent vaccine in maternal antibody positive (MAb+) chickens when challenged with a very virulent plus (vv+) strain of MDV, 648A. The only drawback was that it retained its ability to induce bursa and thymus atrophy (BTA) like that of the parental rMd5 in maternal antibody negative (MAb-) chickens. We recently reported that the attenuated Meq null virus did not induce BTA at 40th cell culture passage onward. Its protective ability against challenge with vv+ MDV, strain 686 was similar to the original virus at 19th passage in MAb- chickens. In this study, we compared the same series of attenuated Meq null viruses in commercial chickens. In commercial chickens with MAb, the attenuated viruses quickly lost protection with increasing cell culture attenuation. These data suggest that although attenuation of these Meq null viruses eliminated BTA, it has no influence on their protective efficacy in MAb- chickens. However, in commercial chickens (MAb+), the best protection was provided by the original l9th passage, the attenuated 40th passage was as good as one of the currently commercial CVI988/Rispens vaccine and it does not induce BTA. Therefore, protection against virulent MDV challenge and induction of lymphoid organ atrophy are simultaneously attenuated by serial passage in vitro.