Fibrocalculous pancreatic diabetes (FCPD) is a form of diabetes associated with tropical chronic calcific pancreatitis, seen mostly in developing countries. FCPD is likely to be a multifactorial disease with both environmental and genetic components. The reg 1A gene encodes a protein associated with regeneration of pancreatic islets and has a sequence identical to that of pancreatic stone protein. Since FCPD is associated with both diabetes and pancreatitis, we tested the hypothesis that FCPD may be the result of mutations in the coding regions of the reg 1A gene. Restriction length polymorphisms (RFLPs) and possible sequence variants of the reg 1A gene were studied by RFLP analysis, looking for single-stranded conformational polymorphisms (SSCPs) and direct nucleotide sequencing. In 20 patients with FCPD and 20 control subjects, no RFLPs were detected using 10 restriction enzymes. In 50 patients with FCPD and 50 control subjects, no SSCP variants were detected. Finally, direct nucleotide sequencing of the reg 1A gene from 30 patients with FCPD did not show any differences from the published human reg 1A gene sequence. In conclusion, it seems unlikely that mutations in the coding region of the reg 1A gene are a common cause of FCPD.