Pseudomelanosis duodeni, speckled black pigmentation of the duodenal mucosa, presents a striking appearance at endoscopy. Among the 14 reported cases there is a predominance of black women greater than 40 years old, but it can occur in any race and age group. There is no known association with pigmentation elsewhere in the gastrointestinal tract or with the use of laxatives. However, most reported patients were hypertensive (many treated with hydralazine and propranolol) and significant numbers suffered from upper gastrointestinal bleeding, chronic renal failure, or diabetes mellitus. The pigment is usually located in mucosal macrophages, in lysosomes. Histochemical studies and electron probe microanalysis suggest that several pigments may result in this endoscopic appearance, including lipomelanin, ceroid, iron sulfide, and hemosiderin. Additional studies, possibly using tissue from surgical resections or autopsies, are needed to determine the etiology and clinical significance of this heterogeneous entity.