A patient with Zollinger-Ellison syndrome appeared initially to respond to cimetidine with a reduction in gastric acid secretion. Symptoms immediately improved but after three days recurred with increasing severity. Intravenous cimetidine had only a short-lived and partial inhibitory effect on the rate of acid production and because of continuing pain and progressive bleeding from his duodenal ulcer, total gastrectomy was performed. Evidence of the effect of atropine and of oral and intravenous cimetidine is presented. Despite recent optimism, cimetidine is not always adequate treatment for Zollinger-Ellison syndrome.