Background: Pancreatic involvement in AIDS is rarely mentioned in medical literature. Aims: To identify the main morphological patterns of the pancreas using optical and electron microscopy in AIDS patients. Design: An open, prospective, and sequential study in a tertiary institutional hospital. Methods: Consecutive post-mortems of 109 AIDS patients and 38 controls (1995). Baseline characteristics of AIDS patients and controls were evaluated. Morphological analysis consisted of: (i) semi-quantitative score of acinar and parenchymal elements; (ii) qualitative analysis of ducts, vascular components, nerves, and Langerhans' islets; (iii) specific stains and immunohistochemistry for opportunistic agents; (iv) ultrastructural data. Results: The mean age of AIDS patients was 37 years; 80% were male; 60% were white; 210/0 were alcoholic. All patients with AIDS had normal blood amylase, blood glucose, and pancreatic ultrasound. Histological findings were: acinar atrophy (60%), few zymogen granula in acinar cytoplasm (52%), abnormalities in acinar nucleus (65%), pancreatic steatosis (66%), and focal necrosis (17%). Immunohistochemistry revealed: mycobacteriosis (22%), toxoplasmosis (13%), cytomegalovirus (9%), Pneumocystis carinii (9%), and HIV p24 antigen in macropahge cytoplasm (22%). Ultrastructural examination showed: decreased zymogen granula, enlargement and proliferation of the endoplasmic reticulum and mitochondria, nuclear abnormalities, and increased lipid droplets in acinar cytoplasm. Conclusion: Pancreatic involvement in AIDS is very frequent (90%) and is usually asymptomatic. Morphological changes showed three patterns of pancreatic alterations: 'nutritional-like', inflammatory and both of these together. The 'nutritional-like' pattern (atrophy, few zymogen granula and steatosis) may be due to many factors such as nutritional characteristics (Kwashiorkor-like) induced by the HIV infection or related to the HIV virus itself. (C) 2000 Lippincott Williams & Wilkins.