Thirteen patients with Zollinger-Ellison syndrome (ZES) were treated with cimetidine. This population could be divided into chronic forms, mostly presenting as a common duodenal ulcer, and acute forms resulting in critical problems requiring intensive medical care. Among the 7 patients with chronic ZES, cimetidine treatment was unsuccessful in 2; satisfactory clinical control was obtained in 3 others, but gastrinoma excision was the final treatment; cimetidine treatment has been prolonged for more than 15 months in the last 2 patients. If, in this condition, acute pharmacologic secretory inhibition were constantly obtained, therapeutic efficiency criteria are not sensitive enough to establish certainty in the patient's long-term follow-up. Total gastrectomy is still a valuable alternative if excision of the gastrinoma is not possible. Of the 6 patients with acute ZES, 4 were treated by pirenzepin (0.5 mg/kg intramuscularly 3 times a day) adjunctive to cimetidine infusion (2.4 mg/day), which resulted in increased antisecretory activity. However, total gastrectomy was the final outcome in every patient, with 1 immediate postoperative death. In conclusion, cimetidine in ZES treatment, although capable of inducing ulcer healing, diarrhea disappearance, and dramatic secretory inhibition, is still challenged by surgery, which allows either complete cure of the gastrinoma or definitive suppression of the secretory virulence.