Five out of nine consecutive patients with HIV-related visceral aspergillosis observed by us since 1984 were diagnosed only at necropsy examination. The histopathological features of these five patients [two with isolated pneumonia, one with central nervous system (CNS) involvement, one with brain abscess and respiratory disease and one with pulmonary, pleural and kidney infection] have been evaluated according to epidemiological, clinical and radiological features. On the basis of our experience, life-threatening aspergillosis, which is often misdiagnosed or missed in the setting of HIV infection and AIDS, should be suspected in patients with far-advanced underlying disease and unexplained signs and symptoms, even in the absence of some presumed risk factors (i.e. neutropenia and prior steroid treatment). Plain chest radiography and bronchoscopy with broncholaveolar lavage may fail to reveal respiratory disease, CNS aspergillosis is not necessarily associated with suggestive neuroradiological features and disseminated disease may present with multiorgan failure. The unfavorable outcome of this emerging AIDS complication can be improved only by earlier diagnosis based on invasive techniques and appropriate and timely treatment.