Animals of 4 families of small wild mammals were live-trapped and inoculated intranasally with Naegleria fowleri to determine patterns of susceptibility. Of the 7 species of animals examined, only rodents were susceptible to N. fowleri. Susceptible animals were eastern gray squirrel, hispid cotton rat, muskrat, and house mouse. Mammals that were not susceptible at a dose of 10(6) were opossum, raccoon, and eastern cottontail rabbit. Perhaps rodents and humans share a common anatomical or physiological determinant that makes them susceptible to infection with N. fowleri.