The marked fluctuation of tetrodotoxin (TTX) contents in pufferfish led us to suspect the exogenous origin of the toxin. Based on a food chain hypothesis, various marine biota were tested for TTX with a fluorometric tetrodotoxin analyzer. Consequently, bacteria were found to be the genetic origin of TT. The survey also revealed the occurrence of new TTX analogs in pufferfish, newts and a frog. Those analogs were isolated and their chemical structures were determined. The analogs provided valuable information on biosynthetic as well as metabolic pathways of TTX and on structure-activity relationship.