In a prospective study 96 patients with esophageal and gastric lesions were investigated by multiple endoscopic biopsy, brush cytology, and guided lavage cytology. The aim was to evaluate the diagnostic accuracy of each of these methods in a prospective study. 50 malignant and 46 benign lesions were found. The final diagnosis was proven by operation or autopsy in 53 cases, by multiple endoscopic follow-up in 31, and by clinical control in 8. No follow-up was possible in 4 patients. The malignant lesions were diagnosed by multilple biopsy in 86.0%, by brush cytology in 84.0%, and by lavage cytology in 50.0%. The diagnostic yield of lavage cytology was thus significantly lower (P less than 0.01). It is concluded that a combination of multiple biopsy and brush cytology is the most valuable aid in endoscopic diagnisis of esophageal and gastric malignancy with a diagnostic accuracy of 96%.