A three year investigation of toxic fish from the Caribbean Sea has led to the discovery of Caribbean ciguatoxin (C-CTX1) and several secondary toxins. C-CTX1 (MH+ 1123.6) was recovered in 1.4 x 10-7 % yield from the muscle tissues of 164 kg Sphyraena barracuda and Caranx latus donated by tournament sports fishermen in St. Thomas, USVI. C-CTX1 was later confirmed by LC/MS in seafoods implicated in 4 independent cases of ciguatera fish poisoning in the eastern U.S. and Caribbean. Spectral data acquired to date distinguish C-CTX1 from its Pacific homologue. Notable differences exist in the alkyl side chain, the number of unconjugated olefins and in the number of bridgehead methyls. The ether-ring skeleton of the Pacific CTX appears to be conserved in the Caribbean form. C-CTX1 is ca. 5-10 fold less toxic that the Pacific homologue in assay systems measuring sodium channel activity. Median inhibitory concentrations are 1.5 nM against synaptosomal sodium channel preparations, and 9.7 pM against mouse neuroblastoma N2A cell cultures.