The sequence of the human laminin β2 chain (previously s-laminin) was derived from cloned cDNAs. The complete translation product has 1798 amino acid residues, including a 32-residue signal peptide. The human chain lacks the tripeptide sequence ILRE in domain I which is present in the rat polypeptide chain and has been shown to promote motor neuronal cell adhesion. The human gene (LAMB2 was localized to chromosome 3p21 using somatic cell hybrids and fluorescent in situ hybridization analysis. Northern and in situ hybridization analyses from numerous fetal tissues revealed that the β2 chain in generally widely expressed. β2, but not β1, was shown by in situ hybridization to be expressed in fetal brain and renal glomeruli. In fetal skin, β2 was expressed both in epidermal and dermal cells, while β1 was expressed only in the dermis. Expression of β2 in fetal liver was seen in hepatocytes, while no signals were observed for β1. In lung, both β1 and β2 were expressed in alveoli and bronchial smooth muscle cells, whereas only the β2 chain was expressed in bronchial epithelial cells. In striated muscle, however, the β1 chain, but not β2 was expressed. These results indicate different biological roles for the laminin β1 and β2 chains.