Using gene targeting in mouse embryonic stem cells, it is possible to introduce diverse mutations into specific genes. Using these methods, various laboratories have reported mutations for a variety of inflammatory cell adhesion molecules including CD18, alpha 5 integrin, ICAM-1, P-selectin, and L-selectin; preliminary reports of other mutations are also available. Mutations in CD18 and ICAM-1 cause impaired inflammatory and immune responses, mutations in P-selectin and L-selectin cause decreased leukocyte rolling and emigration, and a mutation in alpha 5 integrin causes embryonic lethality. Gene targeting complements other approaches for analyzing the function of inflammatory cell adhesion molecules.