The integrin ␣ 7 ␤ 1 occurs in several cytoplasmic (␣ 7A , ␣ 7B ) and extracellular splice variants (␣ 7X1 , ␣ 7X2 ), which are differentially expressed during development of skeletal and heart muscle. The extracellular variants result from the alternative splicing of exons X1 and X2, corresponding to a segment within the putative ligand binding domain. To study the specificity and affinity of the X1/X2 variants to different laminin isoforms, soluble ␣ 7 ␤ 1 complexes were prepared by recombinant coexpression of the extracellular domains of the ␣-and ␤-subunits. The binding of these complexes to purified ligands was measured by solid phase binding assays. Surprisingly, the alternative splice variants revealed different and specific affinities to different laminin isoforms. While the ␣ 7X2 variant bound much more strongly to laminin-1 than the ␣ 7X1 variant, the latter showed a high affinity binding to laminins-8 and -10/11. Laminin-2, the major laminin isoform in skeletal muscle, was recognized by both variants, whereas none of the two variants were able to interact with laminin-5. A specific blocking antibody inhibited the binding of both variants to all laminins tested, indicating the involvement of common epitopes in ␣ 7X1 ␤ 1 and ␣ 7X2 ␤ 1 . Because laminin-8 and -10/11 as well as ␣ 7X1 are expressed in developing skeletal and cardiac muscle, these findings suggest that ␣ 7X1 ␤ 1 may represent a physiological receptor with novel specificities for laminin-8 and -10.