A technique has been developed for assessing the surface hydrophobicity of human gastrointestinal mucosa by measuring the plateau contact angle of saline drops applied to endoscopic biopsy specimens. The plateau contact angle was not affected by the mode of drying. The intraobserver and interobserver coefficient of variation was less than 5%. The gastric mucosal surface had a higher mean contact angle than the submucosal surface (69 degrees vs. 47 degrees, p less than 0.001). Glycerol drops gave lower contact angles than saline drops (55 degrees vs. 69 degrees) but gave the same derived values for surface free energy (42 vs. 41 mJ/m2). Regional values for contact angle were as follows: gastric body 70 degrees, antrum 70 degrees, duodenal bulb 62 degrees (p less than 0.01 vs. stomach), distal duodenum 50 degrees (p less than 0.001 vs. stomach and p less than 0.01 vs. bulb), and rectum 57 degrees (p less than 0.001 vs. stomach). We conclude that it is feasible to measure the surface hydrophobicity of human endoscopic biopsy specimens and that the stomach is relatively more hydrophobic than the duodenum and rectum.