Sixty-five patients with a clinical suspicion of peptic ulcer disease were evaluated with fluid-aided sonography (US). The results were compared with endoscopic and upper gastrointestinal (UGI) series findings. Fifteen normal volunteers were examined by US only. The stomach and duodenum were both adequately visualized in 12 of the normal volunteers and in 51 of the study patients. US detected wall abnormalities in 21 of 23 patients (91%) with abnormal UGI series and endoscopy in the antropyloric and duodenal regions, although none of the 17 documented ulcers were visible by US. Abnormalities detected with US included increased wall thickness (mean, 12.85 mm), asymmetric thickening of the mucosa and muscularis, spasm, and deformity. US was considered normal in 25 of 28 patients (89%) with normal UGI series and endoscopy. The results suggest that US may be a useful nonstressful procedure in the evaluation of peptic ulcer disease previously diagnosed by UGI series or endoscopy.