Precursor mRNAs for proteins that we have called matrix cell adhesion molecules-1 and -2 (Mat-CAM-1 and Mat-CAM-2) were cloned from fibroblasts cultured from a specimen of human abdominal aorta. Both protein sequences have the unusual feature that there is an immunoglobulin kappa (Igkappa)-like domain at the N terminus and they are glycine/proline rich in the C-terminal domain. Antibodies were raised in rabbit against peptides synthesized for a specific unique sequence of Mat-CAM-1 and Mat-CAM-2, respectively (not detected in any other proteins referenced in GenBank). Both antibodies were immunoreactive with adventitial microfibrils of the aorta and some additional arteries. Mat-CAM-1 was detected in the common/internal iliac arteries, but it was not detected in the external iliac artery. Conversely, Mat-CAM-2 was conspicuous in the external iliac artery, but not the common/internal iliac arteries. Thus, these proteins show features of site-specific expression within the arterial tree. Computerized searches show that the genomic origins of Mat-CAM-1 and -2 are in the so-called nasopharnygocarcinoma (NPC) gene on chromosome 2, which is a putative oncogene. Expression of the two different gene products from the same genomic sequence requires shifts of reading frame. Further studies will be required to determine whether these proteins are prototypes for a larger family of tissue-specific matrix proteins arising from alternative transcriptions of the same genomic sequence.