Smoking has an unfavourable effect on peptic ulcer disease. The pathophysiological mechanisms underlying this effect are not known. The enterochromaffin like (ECL) cell is the cellular source of histamine participating in the regulation of acid secretion. The ECL cell is under functional and trophic control of gastrin and the vagus nerves. Nicotine may affect acid secretion through vagal pathways. Furthermore, nicotine may also stimulate neuroendocrine cells. The present study examined if chronic nicotine administration could stimulate the function and growth of the ECL cell. Rats inhaled nicotine vapour at a concentration of approximately 6.2 mumol/m3, 20 hours/day, 5 days/week for 11 weeks. Steady state plasma nicotine concentration was 461.8 (137.5 (SD)) nmol/l. The ECL cell density, histamine content and histidine decarboxylase activity of the oxynitic mucosa were similar to the controls. We also examined the effect of acute nicotine stimulation on the acid output and histamine release from the totally isolated vascularly perfused rat stomach. Nicotine did not stimulate acid secretion or histamine release. Thus no evidence could be provided to support the hypothesis that nicotine exerts its negative effects on peptic ulcer disease by stimulating the ECL cell.