Lipid accumulation has been described in the duodenal lamina propria of human immunodeficiency virus (HIV)-infected patients with diarrhea and malabsorption. Using light and electron microscopy, we studied duodenal biopsies obtained from 54 consecutive HIV-infected patients by means of upper gastrointestinal endoscopy after an overnight fast. The presence of diarrhea and weight loss were recorded, and all the patients had standard stool study for ova, parasites, and bacteria. Serum levels of albumin, triglycerides, and cholesterol were obtained within one week of the endoscopy. Fecal fat and fecal alpha 1-antitrypsin clearance were measured in 11 patients. Lipid accumulation was observed in nine patients (16.6%). Fat droplets were seen in enterocytes, in their basolateral membrane spaces, and in the lamina propria. The mean serum levels of triglycerides (1.85 +/- 0.20 mmol/liter) and cholesterol (2.81 +/- 0.30 mmol/liter) were significantly lower in the patients with enteric steatosis than in patients without this anomaly (respectively, 3.38 +/- 0.39 and 3.97 +/- 0.18 mmol/liter, P < 0.001 P < 0.01). The mean amount of fecal fat in the three patients with lipid accumulation (16 +/- 1.60 g/24 hr) was significantly larger than in the eight patients without lipid accumulation (4.50 +/- 0.62 g/24 hr, P < 0.01). These findings suggest that fat malabsorption in HIV-infected individuals is due to a blockage of transport through the duodenal mucosa. The frequency of diarrhea, weight loss, or identified enteric pathogens did not differ significantly between patients with and without enteric steatosis. Both the etiology and the pathophysiology of these alterations remain to be documented.