Aquaculture feeds for carnivorous finfish species have been dependent upon the use of fish meal as the major source of dietary protein; however, the increasing demands upon the finite quantity of this high-quality protein source requires that feeds become increasingly comprised of alternative plant and/or animal protein. Soybean meal has been has been used to partially replace fish meal in the diets of several fish but it is known to cause enteritis in Atlantic salmon, Salmo salar. We have compared two groups of juvenile (207.2 ± 6.6 g) Atlantic halibut, Hippoglossus hippoglossus, L., fed diets containing fish meal (FM; control) or 30% soybean meal (SBM; experimental) as a protein source for 3 weeks. No detectable difference in feed intake or palatability was evident with the SBM diet relative to the FM diet. Histological examination of the distal intestine was performed to examine leukocyte infiltration of the lamina propria and other changes in morphology commonly observed with soybean-induced enteritis of salmonids. No significant difference was found between fish fed the FM and SBM diets. Global gene expression profiling performed using a high-density oligonucleotide microarray containing 9260 unique features, printed in quadruplicate, from Atlantic halibut revealed subtle underlying changes in the expression of several immune genes and genes involved in muscle formation, lipid transport, xenobiotic detoxification, digestion and intermediary metabolism. These results indicate that SBM can be used successfully as a replacement for animal protein in diet for juvenile Atlantic halibut, although long-term effects on the immune system may ensue. Crown Copyright © 2009. ; peer reviewed: yes ; NRC Pub: yes