Enterostatins, pentapeptides represented at the amino-terminus of the procolipase molecule, are derived following tryptic cleavage of the procolipase molecule in the lumen of the gut. Val-Pro-Asp-Pro-Arg or VPDPR is one such enterostatin. Despite pharmacologic studies suggesting a role for VPDPR in appetite regulation and insulin secretion, the function of this endogenous peptide has been impossible to discern due to the lack of a suitable assay. Using polyclonal antibodies raised against VPDPR and different chromatographic methods, we examined the nature and distribution of enterostatin-like immunoreactivity in rat plasma. The results reported here show for the first time the presence of VPDPR-like immunoreactivity in rat plasma. Further characterization of the plasma VPDPR-like immunoreactivity revealed that a) it is not due to APGPR, VPGPR, or VPDPR but to another peptide similar to VPDPR, and b) plasma VPDPR-like immunoreactivity may circulate bound to large carrier proteins.