Naegleria fowleri, a free-living ameboflagellate, is the causative organism of primary amebic meningoencephalitis. Intransal inoculation of N. fowleri in mice produces an infection similar to human disease. Mice immunized with live N. fowleri by intraperitoneal injection were found to be more resistant to subsequent intranasal challenge. The survival rate was 27% in immunized animals, compared to 0% in the control group. These results may provide a lead to the development of immunotherapy for this virulent disease for which satisfactory chemotherapy is presently unavailable.