Cadherins are integral membrane glycoproteins that mediate calcium-dependent, homophilic cell-cell adhesion and are implicated in controlling tissue morphogenesis. T-cadherin is anchored to the membrane through a glycosyl phosphatidylinositol (Ranscht B, Dours-Zimmermann MT: Neuron 7:391-402, 1991) and expressed in a restricted pattern in developing embryos (Ranscht B, Bronner-Fraser M: Development 111:15-22, 1991). We report here the molecular and functional characterization of the T-cadherin isoform, T-cadherin 2 (Tcad-2) and the expression of the corresponding mRNA. Tcad-2 cDNA differs in its 3' nucleotide sequence from T-cadherin cDNA and encodes a protein in which the carboxy terminal Leu of T-cadherin is substituted by Lys and extended by the amino acids SerPheProTyrVal. By RNase protection, mRNAs encoding the T-cadherin isoforms are coexpressed in heart, muscle, liver, skin, somites, and in neural tissue. Many tissues contain both T-cadherin and Tcad-2 mRNAs in conjunction with N-cadherin transcripts, and T-cadherins and N-cadherin proteins are coexpressed on the surface of individual neurons in vitro. Expression in Chinese hamster ovary cells (CHO) revealed that Tcad-2 is a glycosyl phosphatidylinositol-anchored membrane protein that functions in calcium-dependent, homophilic cell adhesion. The identification of a functional T-cadherin isoform and the coexpression of T-cadherins and N-cadherin by individual cells suggest that specific adhesive interactions of embryonic cells may involve a complex interplay between multiple cadherins.