We have previously shown that the pancreatic stone protein (PSP) is an inhibitor of calcium carbonate crystal growth and may participate in the stabilization of the normally supersaturated pancreatic juice. Our aim in this study was to determine if PSP is a normal secretory product of the human pancreas by determining if the normal human pancreas contains a messenger RNA coding for PSP. Human pancreatic messenger RNAs were used to direct protein synthesis in a cell-free translation system. Immunoprecipitation of translation products with a monospecific antibody directed against the PSP yielded a product migrating as a single homogeneous band on sodium dodecyl sulfate-polyacrylamide gels. This product has a molecular weight of 16,000, the value expected for pre-PSP. Products selected by immunoprecipitation with antitrypsin-1 antibodies also migrated as a single band, with a molecular weight of 27,000. It is concluded that a messenger RNA coding for pre-PSP, distinct from the messenger RNA coding for pretrypsinogen, is present in human pancreas. These results support the hypothesis that PSP is a molecular entity, and not a degradation product of trypsinogen 1 or another pancreatic protein.