The integrin subunit (β1) is common to a group of plasma membrane glycoprotein heterodimers that include the fibronectin, laminin and collagen receptors. These receptors span the plasma membrane, providing a transmembrane linkage between the extracellular matrix and the cytoskeleton. Here, we describe a variant of the human β1 differing from the previously described β1 in the cytoplasmic domain. The variant β1 transcript (β1^3′v is present in different cell types and is synthesized at lower levels compared to the β1 mRNA. The cytoplasmic domain of the β1^3′v is characterized by a unique 12-amino acid C-terminal sequence. A Tyr residue present in this region, and known to be phosphorylated in the β1, is no longer part of a consensus sequence for phosphorylation by Tyr kinases. The integrin cytoplasmic domain anchors actin fibrils to the plasma membrane by interacting with cytoskeletal proteins such as talin and fibulin. The integrin β1^3′v with the variant cytoplasmic domain is likely to mediate a new type of membrane-cytoskeleton interaction during cell-cell and cell-matrix adhesion. Analysis of genomic clones showed that the new sequences of the variant mRNA are identical to an intron located between the last two exons of the β1 gene, indicating that the alternative message is generated either by premature transcription termination or by lack of splicing at this site.