OBJECTIVE Peptides of the chromogranin family occur in peptide hormone-producing cells throughout the body. One source of such peptides is the enterochromaffin-like (ECL) cells, which constitute the predominant population of endocrine cells in the fundus (the acid-producing part) of the rat stomach. The purpose of this study was to examine whether ECL cells, which are controlled by gastrin, represent a major source of circulating pancreastatin, a fragment of chromogranin A. METHODS Rats underwent surgical procedures and treatments in which the ECL cells could be manipulated. The procedures included antrectomy, fundectomy, and gastrectomy (and adrenalectomy), and the treatments included fasting or feeding, gastrin-17 infusion, and administration of omeprazole or ranitidine. The concentrations of pancreastatin-like immunoreactivity (LI) and gastrin in the serum were determined by radioimmunoassay. RESULTS The serum pancreastatin-LI concentration was lowered by about 80% by fundectomy and gastrectomy; both of these procedures eliminated the ECL cell population. Adrenalectomy had no effect on the serum pancreastatin-LI concentration. Gastrin infusion, which activates the ECL cells, promptly increased serum pancreastatin-LI concentration. Refeeding after fasting and administration of omeprazole or ranitidine increased the serum pancreastatin-LI concentrations; these responses were prevented by antrectomy. CONCLUSIONS The concentration of circulating pancreastatin-LI reflects the activity of the ECL cells and the size of the ECL cell population in the rat stomach.