Present study was undertaken to elucidate the changes of the ultrastructure of Naegleria fowleri trophozoite in brain tissue of mice and culture medium. Naegleria fowleri, 0359 strain, which used in this study was cultured in axenic liquid medium, CGVS medium. Each mouse was inoculated with 1 x 10(5) amoebas intranasally under secobarbital anesthesia, and sacrificed on 7th day after the infection. Comparative observation of the ultrastructure of the amoebas in axenic culture and experimentally infected mice brain was done with transmission electron microscope. The results are summarized as follows: 1. The amoebas in mouse brain tissue were round in outline, whereas those of amoebas from axenic culture showed irregular appearance. 2. Mitochondria in the amoebas from axenic culture was oval, round and cylindrical shape and darkly stained, whereas those of the amoebas from mouse brain tissue showed dumbbell shape together with above forms. The stain was not unique, but light and/or dark. 3. Rough endoplasmic reticulum of amoebas in brain tissue was tubular, but from culture it was vesicular or tubular in shape. 4. Empty vacuoles were demonstrated in amoebas from culture, while food vacuoles with myelinated structures were abundant in those from tissue, suggesting a strong phagocytic activity. 5. Mouse brain tissue infected were extensively destroyed, and polymorphonuclear leukocytes were infiltrated predominantly with inflammatory lesion. Amoebas were observed in the vicinity of the capillary.