Two patients had systemic mastocytosis and histamine excess, marked gastric acid and pepsin hypersecretion, and diarrhea. Cimetidine inhibited gastric acid secretion in both, but with only partial initial control of diarrhea. The other manifestations of mastocytosis were only partly controlled, even by combined H-1 and H-2 antagonist therapy. Basal and pentagastrin-stimulated acid and pepsin secretion before and after 5 and 14 months, respectively, of continuous and effective cimetidine therapy were essentially the same. Thus there was no evidence for an increase in the number of H-2 receptors during the long period of blockade or of involution of the parietal or peptic cell mass.