Quantitative trait loci involved in the primary antibody response to keyholelympet hemocyanin (KLH) and Mycobacterium butyricum were detected in twoindependent populations of laying hens. The first population was an F2 cross(H/L) of lines divergently selected for either high or low primary antibodyresponses to SRBC, and the second population was an F2 cross between 2commercial layer lines displaying differences in feather pecking behavior (FP).Both populations were typed with microsatellite markers widely distributed overthe genome with similar intervals between markers. Titers of antibodies bindingKLH and M. butyricum were measured for all individuals by ELISA. Two geneticmodels were applied to detect QTL involved in the humoral immune response: ahalf-sib model and a line-cross model, both using the regression intervalmethod. In the half-sib analysis, 2 QTL (on GGA14 and GGA27) were detected forthe antibody response to KLH for the H/L population, and 2 QTL (on GGA14 andGGA18) were detected for the FP population. Only 1 QTL was detected for M.butyricum on GGA14 in the FP population using the half-sib analysis model. TwoQTL were detected for the FP population on GGA2 and GGA3 using the line-crossanalysis model. A QTL for the primary antibody response to KLH detected on GGA14was validated in both populations under the half-sib analysis model. The presentdata suggest differences in the genetic regulation of antibody responses to twodifferent T-cell dependent antigens.