The acquisition of invasiveness of mammalian tissue by free living amoebae (FLA) is an extremely noteworthy phenomenon. Many factors may be responsible for this evolutionary change in their physiology. The present work aimed to clarify the host factors in this problem. Albino mice were the laboratory animals used in this work. Non-pathogenic strains of FLA were isolated from ear, nose and pharyngeal swabs and from contact lenses of patients attending out patient clinics in Benha University Hospitals. Isolation was done by cultivation of non-nutrient agar at 37 & 43 degrees C and identification was made by flagellation test. The degree of pathogenicity of isolated strains was assessed by using animal pathogenicity test. Endoxan (0.7 mg/kg) and Prednisolone (2 mg/kg) were used for 15 days orally to suppress the immunity of clean mice before their inoculation intranasally with the isolated strains. All groups were observed for 3 weeks post-infection. Mortality rates recorded were higher in Endoxan or Prednisolone treated and Naegleria infected groups A I & B I (20 & 15% respectively) than Endoxan or Prednisolone treated and acanthamoeba infected groups A II & B II (10%) and drug control (10%). Histopathological examination of brain and meninges revealed severe changes in form of severe meningoencephalitis, severe vacuolar degeneration, and moderate haemorrhage and necrosis in brains of groups AI & BI and less severe changes in groups AII & BII (10%) form of-non granulomatous encephalitis. Drug control groups showed negligible changes. Great attention must be paid to reveal the presence of FLA before using immunosuppressive drugs in human cases.