We have cloned the gene for a novel LIM-domain protein from human fibroblasts whose expression is substantially decreased in simian-virus-40-(SV40)-transformed cells. This protein has a calculated molecular mass of 61 kDa and comprises a proline-rich domain followed by three LIM motifs. It appears to be identical to the focal adhesion protein p83 that has recently been isolated and characterized from porcine and human platelets. Hybridization experiments demonstrate a very low degree of evolutionary conservation of its sequence between mammals and birds. It is therefore possible that the novel protein represents the human equivalent of the chicken protein zyxin as the two proteins display a very similar overall structure, although their amino acid sequences diverge markedly from each other. The repression of this zyxin-related protein in virally transformed fibroblasts may explain, at least in part, the dramatic morphological changes that occur at the cell surface and in the cytoskeleton of transformed cells.