Two patients with high-output gastrocutaneous fistulas were treated with total parenteral nutrition and gastric antisecretory drugs. IV administration of omeprazole decreased acid output in one patient in a rapid and significant way, resulting in the spontaneous healing of the fistula after eight days of treatment. In the second patient, omeprazole caused a marked reduction in the acidity of the fluid in the fistula, which also closed without surgical operation. The long-standing decrease in acid output induced by intravenous omeprazole may be very useful for promoting spontaneous closure of high-output gastrocutaneous fistula.