In this paper we report two incidents of ciguatera fish poisoning (CFP) that occurred in 2008 on Kakeroma Island in Kagoshima Prefecture, Japan. A family consisting of father (42 y.o.), mother (39 y.o.), daughter (11 y.o.) and son (6 y.o.), as well as a friend of the family (male, 78 y.o.) consumed sliced flesh (sashimi) and developed typical symptoms of CPF 4-5 h later: diarrhea, vomiting, and paresthesia of the extremities. Additionally, the two male adults (42 and 78 y.o.) developed mild hypotention (84/48 and 94/40 mmHg, respectively) and bradycardia (36 and 50 bpm, respectively) and were rushed to the ER of the nearest hospital, located on an adjacent island. The implicated fish were caught together off the west coast of the island and were identified as Variola louti and Lutjanus monostigma based on analysis of 16S rRNA gene coded on mtDNA. Remnants of the implicated fish and other fish caught on the same occasion were examined by the official mouse bioassay method (MBA), which defines the minimum amount of CFP toxin needed to kill a male mouse of ddY strain of 20 g body weight within 24 h as one mouse unit (MU). A significantly high toxicity was detected in the V. louti (0.2 MU/g) eaten by the family and the L. monostigma (0.8 MU/g) eaten by the elderly man. Other specimens of Lethrinus nebulosus, Variola albimarginata, Lutjanus gibbus (2 specimens), Aphareus rutilans, and Sphyraena forsteri (2 specimens) were found to be nontoxic (< 0.025 MU/g). The medical records regarding island inhabitants (ca. 1,500) kept at Kakeroma Tokushukai Clinic, the only medical facility on the Island, and also at Setouchi Tokushukai Hospital, a nearest hospital on an adjacent island (Amami) revealed 6 CFP outbreaks involving 13 cases between 2005 and 2008. The estimated frequency of CFP was 10.0 incidents/10,000 persons/year and the morbidity rate was 21.7 cases/10,000 persons/year. The symptoms and signs observed in the patients and the implicated fish species, L. monostigma and V. louti, were typical of CFP in this region.