Sero-epidemiologic survey has been carried out to establish serologically the presence of hantavirus in areas of South Africa. The survey was oriented to search natural infection in both of humans and wild rodents and involvement of human disease. The normal human sera were collected from the residents in urban and rural areas of Western Cape, and rural area of Eastern Cape province. The rodent sera came from various species of rodents trapped in Northern Cape and Western Free provinces. The patient sera were selected from the patients of renal failure, pulmonary syndrome and pyrexia of unknown origin (PUQ) according to diagnostic chart among the patients hospitalized in major hospitals of Cape Town area. The sera were screened and titrated by IFA test using antigens of Hantaan (HTN), Seoul (SEO), Puumala (PUU), and Prospect Hill (PH) viruses primarily. Positive cases were subjected to differential IFA test using HTN, PUU and PH antigens and plaque reduction neutralization test for further confirmation. Anti-hantavirus antibodies were detected from 2 of 352 rural, 1 of 172 urban residents of E. Cape, and 5 of 118 rural, 5 of 368 urban residents of W. Cape. The antibody was also demonstrated from 5 of 221 wild rodents, and it was appeared that 2 different species, Aethomys namaquensis and Tatem leucogaster, are involved. Among 318 patients tested, 3 who were diagnosed as chronic renal failure, acute respiratory distress syndrome (ARDS) and glomerulonephritis were proved to be positive. The reaction patterns obtained from all of these positive sera were distinct from hantaviral sero-patterns ever established. This result suggests that new viruses may exist in this area and play an possible etiologic role in human disease. The feature of serologic survey on anti-hantavirus antibody demonstrable newly from African wild rodents which are different from reservoir species in other continents elicits a conjecture that the virus may be different from known hantaviruses ever found. This fact also suggests that an expanded role in etiologic involvement with other unknown human diseases by newly emerging hantaviruses may be possible in this areas.