A 65 kDa-tumor-associated protein (p65) was isolated from human and rat carcinoma cell culture media. Antibodies raised to the rat protein recognized an antigenically related protein in human cancer cell line. 2. Amino acid composition, N-terminal and internal sequence as well as peptide map and western blot analysis of the p65 strongly suggest a high degree of homology between the human and rat p65 proteins. 3. Homology searches indicated that p65 was not homologous to previously sequenced proteins, but that it may be related to proteins of the steroid receptor superfamily of genes, especially c-erb A gene.