Background: Endoscopic minimally invasive therapy for submucosal tumors of the gastrointestinal tract by use of endoscopic ultrasound has not yet come into widespread use, and this technique has not been fully evaluated. We therefore investigated this method of treatment in patients with gastrointestinal submucosal tumors. Methods: Forty-five patients with suspected gastrointestinal submucosal tumors (esophagus [5], stomach [1], duodenum [16], colon [23]) based on barium enema studies and endoscopy underwent endoscopic ultrasound by the water-filled or balloon method. The layer of origin and the internal echogenicity of the lesions were evaluated. After confirming that the tumors were submucosal, the lesions were resected using injection of physiological saline solution and electrocautery. Results: Using a one-channel or two channel method, all tumors were completely resected without serious complications and the diagnosis was histologically confirmed. Ulceration at the site of resection healed within 2 to 4 weeks (mean 23 days) and there has been no local recurrence. Conclusions: Our technique of endoscopic submucosal tumorectomy appears to be a safe and useful diagnostic-cum-therapeutic procedure for gastrointestinal submucosal tumors.(Gastrointest Endosc 1997;46:311-7)