The ciguatoxins are lipid soluble polyether compounds which have structural and biochemical features in common with the brevetoxins. Pure ciguatoxin-1, ciguatoxin-2 or brevetoxin-2 added to water containing Gambusia affinis induced similar signs, including pronounced opercular movement and uncoordinated swimming preceding death. The estimated LD50s (48 hr) to G. affinis for ciguatoxin-1, ciguatoxin-2 and brevetoxin-2 were 0.5, 2.1 and 10 nmoles/litre, respectively, indicating that the ciguatoxins were up to 20-fold more potent than the brevetoxins in this assay. Previous studies reveal that the ciguatoxins are more potent than the brevetoxins in both i.p. lethality to mammals and affinity for voltage-dependent sodium channels. However, relative to their affinity for the voltage-dependent sodium channel, brevetoxin-2 is 4-fold more potent to fish than the ciguatoxins, whereas the ciguatoxins are up to 11-fold more potent to mice than brevetoxin-2. This study found that only 3.4% of administered ciguatoxin-1 was accumulated by G. affinis. Ciguatoxin-1 may be biotransformed by G. affinis. The lethal effects of the ciguatoxins in fish may impose an upper limit on the levels of ciguatoxin carried by fish, which could contribute to the low incidence of human fatality associated with ciguatera.