Abstract. This study evaluated bacterial skeletal disease in conjunction with the major histocompatibility complex (MHC) in a genetically pure line of broiler breeder chickens. Chickens from six broiler breeder flocks were examined for skeletal lesions, bacterial pathogens, and MHC genotype. During a 10-week period, eightyeight, 9-to 21-week-old lame chickens and 34 normal, age-matched controls were selected. Tenosynovitis, arthritis, and femoral or tibiotarsal (or both) osteomyelitis occurred in 86 of 88 (97.7%) lame chickens. Ninetyfive bacterial isolates were obtained from 83 of 88 (94.3%) lame birds and 4 of 34 (11.8%) controls. Staphylococcus spp. was isolated from 72.6% of the skeletal lesions, predominantly Staphylococcus aureus (38.9%). MHC B complex genotypes were determined by hemagglutination for 88 lame birds, 34 controls, and 200 randomly selected birds from each of the six flocks (1,200 total). Combined chi-square analysis revealed that the homozygous MHC genotypes B A4/A4 ( 2 ϭ 14.54, P ϭ 0.0063) and B A12/A12 ( 2 ϭ 42.77, P ϭ 0.0001) were overrepresented in the sample of symptomatic birds compared with random samples from the same flocks. The homozygous A4 and A12 MHC genotypes influenced flock chi-square values more than the corresponding heterozygotes. An MHC B complex influence on bacterial skeletal disease was apparent in this line of broiler breeders.