Endoscopic ultrasound (EUS) was performed in 37 patients with upper gastrointestinal tract submucosal tumors (SMT). Fourteen of these were located in the esophagus, 20 in the stomach, and 3 in the duodenum. In 26 patients histologic confirmation was achieved by operation (n = 15) or biopsy/puncture (n = 11). EUS was able to visualize all tumors and, with one exception, determined their originating wall layer correctly. It became evident that myogenic tumors arise from the echo-poor layers (second layer and fourth--that is, muscularis propria) and that other lesions, such as cysts or fibromas, originate from the third, echo-rich layer (submucosa). Tumor size was correctly (+/- less than 5 mm) predicted in 87% of cases. Computed tomography, performed in 22 patients, was successful in visualizing the SMT in only two-thirds of cases. No single endosonographic criterion could be obtained which enabled accurate differentiation between benign and malignant SMT. However, from a clinical point of view, it seems reasonably safe to regard smaller (less than 3 cm), smoothly demarcated SMT as benign and follow them up by repeated EUS, especially in patients at risk for surgery. Larger masses (greater than 5 cm) and those with irregular borders should be suspected of being malignant. In the future, application of new, small ultrasound probes that can be used during conventional endoscopy (two SMT were visualized successfully) may greatly simplify the procedure.