Immunoreactivities of several natural and synthetic secretins were investigated using a newly developed radioimmunoassay. It was found that weight for weight immunologic activities of the purest natural (Mutt) and synthetic (Squibb) secretins were indistinguishable. Compared to Squibb secretin, on a weight for weight basis, immunoreactivity of semipurified synthetic Schwarz/Mann secretin exceeded its bioactivity. This suggested contamination of Schwarz/Mann secretin with immunologically cross-reacting but biologically inactive peptide fragments. Immunoreactivity of crude Sigma secretin was found to be about 104 times less than that of Mutt secretin. The commercially available pure porcine secretin/cystein-HCl mixture (Jorpes) was found to be stable and to contain the equivalent of 21 µg of pure porcine secretin per ampule. After calibration against Squibb or Mutt secretin it can be used as reference standard in the secretin radioimmunoassay. 1 This work was supported in part by grants from U.S. Public Health Service, Research Grant No. 5 MOI RR 349, National Institutes of Health, General Clinical Research Centers Branch.