Genetic improvement for resistance to Marek's Disease (MD) in chickens continues to be of interest to the poultry industry. The aims of this study were to identify effects of the MHC on the molecular level and of avian leukosis virus (ALV) resistance status on MD mortality in two noninbred White Leghorn chicken lines that differ in B blood group type. Previously, within each of the chicken lines, sublines had been selected for resistance or susceptibility to ALV infection with Subgroups A and B. In this study, F2 offspring, obtained by crossing the two ALV-resistant or the two ALV-susceptible sublines, were tested for MD mortality after contact exposure at 1 d of age. Reciprocal matings were made in the grandparental generation. The MD mortality percentages, in an observation period of 17 wk, of F2 offspring from two hatches were 82.63 and 92.35%, respectively. Survival analysis (Cox model) was applied to assess the risk of dying from MD. No differences in MD mortality risk profiles were found between ALV-resistant and ALV-susceptible F2 offspring. Within ALV-susceptible F2 offspring, however, a reciprocal mating effect was observed in both hatches. The MHC Class I, II, and IV restriction fragment length polymorphism (RFLP) analyses were carried out on birds of the first hatch. Although two of 11 MHC class IV RFLP bands displayed a significant effect, in general, a strong association of MHC and MD mortality was not detectable.