Clonidine-displacing substance (CDS) from brain is biologically active in the kidney and stomach and on platelets. To determine whether CDS is contained in these and other peripheral tissues, homogenates of fresh brain, eight other organs and serum from rat were ultrafiltered (less than 10,000 mol. wt only), dried and extracted with methanol. Evaluation by radioimmunoassay (RIA) using antibodies to p-aminoclonidine showed that adrenal gland and gastric fundus (GF) contained significantly greater amounts of CDS-like radioimmunoactivity than brain; intermediate-to-low activity was present in heart, small intestine, serum, kidney and liver; lung and skeletal muscle values were near-background. RIA-positive extracts elicited well-correlated contractile activity in a GF smooth muscle bioassay; contractions persisted in the presence of antagonists of various transmitters and modulators, but were abolished by low concentrations of the calcium channel blocker verapamil. Serum levels of CDS were profoundly reduced following removal of the adrenal glands. We conclude that a CDS-like substance is present not only in brain as previously reported, but also in peripheral organs and in the circulation.