Using the differential screening technique, a cDNA related to the mammalian family of lipid transfer/lipopolysaccharide-binding proteins was cloned from the Atlantic cod (Gadus morhua L.). The gene is an ortholog of a recently identified gene of rainbow trout (Oncorhynchus mykiss). Phylogenetic analyses suggest that teleost BPI/LBP are modern descendants of the ancestor of mammalian bactericidal/permeability-increasing protein (BPI) and lipopolysaccharide-binding protein (LBP), and a gene of the urochordate Ciona intestinalis is related to this gene family. Molecular modeling suggests that the structure of cod BPI/LBP is similar to mammalian BPI and LBP, while its highly basic character is similar to BPI. Cod BPI/LBP is constitutively expressed in head-kidney (HK) leukocytes. After intraperitoneal injection of bacterin high levels of cod BPI/LBP mRNA were detected also in peripheral blood cells and spleen, while moderate to low levels of transcript were found in heart, liver, gills, skin, brain, and intestine. We conclude that the patterns of charge and expression of cod BPI/LBP are more similar to mammalian BPI than to mammalian LBP.