The pancreatic polypeptide cell, the only mature endocrine cell in the fetal pig pancreas, produces equimolar amounts of two peptides, pancreatic polypeptide and pancreatic icosapeptide, from the same precursor. The amino acid sequence of pancreatic polypeptide is more homogeneous among species, whereas pancreatic icosapeptide is heterogeneous. We determined the 19-amino acid sequence of porcine pancreatic icosapeptide, which is markedly different from that of known sequences (e.g. 47% homology with human). We developed an ELISA that can measure porcine pancreatic icosapeptide levels in the range of 7.2-480 pmol/liter. Actual levels of pancreatic icosapeptide in pig sera were 9.6-25 pmol/liter. The assay requires relatively small amounts of nonextracted samples, and human and mouse sera do not cross-react. Levels of pancreatic icosapeptide rose in response to hypoglycemia in pigs and to carbachol in fetal porcine pancreatic cells in vitro. When fetal porcine pancreatic tissue was transplanted into nonobese diabetic-severe combined immune deficiency mice, porcine pancreatic icosapeptide (but not C peptide) was detectable in mouse sera for up to 3 wk after transplantation, with levels highest on d 4. Porcine pancreatic icosapeptide and insulin were detectable in grafts removed from the mice. Therefore, porcine pancreatic icosapeptide may be used as a marker of the viability of xenotransplanted fetal pig pancreatic tissue in the immediate posttransplant period.