Penicillium marneffei is a rare human pathogen predominantly affecting residents of South-east Asia. We report four fatal cases from Hong Kong in human immunodeficiency virus-infected patients. The diagnosis was established by histological examination and confirmed by isolation of the fungus. The infection was disseminated with involvement of lymph nodes, liver, spleen, lung, intestine and bone marrow. The involved organs showed an exclusively anergic tissue reaction characterized by a diffuse infiltrate of fungi-laden macrophages, multiple co-existing opportunistic infections and lymphoid cell depletion. This organism has to be distinguished from Histoplasma capsulatum and Pneumocystis carinii. Establishment of the diagnosis is important not only because this infection is potentially curable, but also it is a likely indicator disease of AIDS in South-east Asia. Penicilliosis marneffei should be suspected in any symptomatic HIV-positive patient who comes from or has visited endemic areas of South-east Asia.