Background: Kaliondeonde is an AIDS-like immunosuppressive illness of unknown etiology common in Zambia and Malawi. It has similar, but not identical, symptoms to HIV/AIDS, and appears to have been in south central Africa longer. It is often viewed by both the public and academics as being the same as HIV/AIDS. Method: Research was conducted in Zambia among seven kaliondeonde patients to determine the perceptions of the sickness, and the symptoms of the disease, in comparison with HIV/AIDS. A subset of four of the patients were examined by both a traditional healer and a physician, and tested for HIV. Results: Two of the four kaliondeonde patients were found to be HIV negative, suggesting the possibility that kaliondeonde is different from HIV/AIDS. Conclusions: If future research confirms that many kaliondeonde patients are in fact HIV-negative, it will become vitally urgent to clarify the distinctiveness of the two illnesses and alter perceptions and knowledge of kaliondeonde prevention, epidemiology, etiology, and clinical practices.