Marek's disease virus (MDV) encodes a basic leucine-zipper protein, Meq, that shares homology with the Jun/Fos family of transcriptional factors. Conclusive evidence that Meq is an oncogene of MDV came from recent studies of a Meq-null virus, rMd5 Delta Meq. This virus replicated well in vitro, but was non-oncogenic in vivo. Further characterization of this virus in vivo indicated that the meq gene is dispensable for cytolytic infection since it replicated well in the lymphoid organs and feather follicular epithelium. Since rMd5 Delta Meq virus was apathogenic for chickens, we set out to investigate whether this virus could be a good candidate vaccine. Vaccine efficacy experiments conducted in Avian Disease and Oncology Laboratory (ADOL) 15I(5)x 7(1) chickens vaccinated with rMd5 Delta Meq virus or an ADOL preparation of CVI988/Rispens indicated that the Meq-null virus provided protection superior to CVI988/Rispens, the most efficacious vaccine presently available, following challenge with a very virulent (rMd5) and a very virulent plus (648A) MDV strains.