Twenty-five patients with AIDS and esophageal symptoms were evaluated for the presence of esophageal disease and human immunodeficiency virus type 1 (HIV-1) in the esophageal mucosa. A single infectious process caused by Candida albicans, cytomegalovirus, herpes simplex virus, varicella-zoster virus, or Mycobacterium avium-intracellulare complex or a single noninfectious process caused by Kaposi’s sarcoma or reflux esophagitis was identified in 20 patients. Two processes were identified in 5 patients. HIV-1 mRNA was detected by in situ hybridization in mononuclear cells in esophageal lamina propria in 36% of patients. The presence of HIV-1 in the esophageal mucosa was not associated with a specificesophageal symptom, mucosal inflammation or ulceration, Kaposi’s sarcoma, specificopportunistic infection, or response ofthe infection(s) to therapy. Esophageal disease in patients with AIDS appears to be associated with specific pathologic processes rather than the presence of HIV-1 in esophageal mucosa. © 1993 by The University of Chicago.