BACKGROUND The inhalation form of anthrax, although rare, is nearly always fatal because of the rapid progression of the disease with little host response until the terminal stages of the disease. The Gulf War heightened the concern that anthrax could be used as a biologic weapon. Past studies modeling pathologic changes in human inhalation anthrax have used the rhesus monkey. METHODS We studied pathologic changes in the rhesus monkey model of inhalation anthrax. Gross examination as well as light and electron microscopy were used to define pathologic alterations. Immunolabeling techniques were used to identify the anthrax bacillus by light and electron microscopy. RESULTS Gross changes included hemorrhage in mesenteric (54%) and tracheobronchial (46%) lymph nodes, meninges (38%), lungs (31%), and small intestinal serosa (31%). Histopathologic changes included suppurative meningitis (77%); hemorrhages in the meninges (54%), neuropil (31%), and pulmonary alveoli (31%); and pneumonia (15%). Spleens and various lymph nodes from all monkeys had one or more of the following changes: hemorrhage, acute inflammation, extracellular bacilli, lymphocytic depletion, and histiocytosis. Spleens of two monkeys were devoid of extracellular bacilli, but degraded intrahistiocytic bacilli reacted with Ab to Bacillus anthracis cell wall polysaccharide. CONCLUSIONS In our study, compared with previous reports, meningitis and mesenteric lymph node hemorrhages were more common, whereas mediastinal and tracheobronchial lymph node hemorrhages were less common. Immunostaining highlighted intracellular bacilli that would have been otherwise missed by light microscopic examination.