In commercial pure white leghorn lines, A, B, and C, the effects on resistance against a virulent strain of Marek's disease virus were assessed for B19 and B21 haplotypes of the chicken major histocompatibility complex. B haplotypes were identified by direct hemagglutination using alloantisera raised against erythrocyte antigens. In homozygous B21 female chicks from lines A and B, mortality upon challenge with virus was 16% and 9%, respectively; in B19 chicks, mortality was 42% and 60%, respectively. Intermediate mortality was observed in heterozygous B19/B21 birds. When line A and B hens were crossed with B15/B15 or B5/B19 cocks from line C, differences between B19 and B21 were significant only in the progeny from B5/B19 sires. Therefore, it was concluded that selection for major histocompatibility complex-associated disease resistance markers may be useful only when B haplotypes complement each other in commercial line crosses and when interactions with genetic background do not severely obscure the differential haplotype effects, as are observed within pure lines.