Ciguatoxins (CTXs), produced by toxic benthic dinoflagellates, can bioaccumulate in marine organisms at higher trophic levels. The current study evaluated the uptake and depuration kinetics of some of the most potent CTXs, Pacific CTX-1, -2, and -3 (P-CTX-1, -2, and -3), in orange-spotted grouper (Epinephelus coioides) exposed to 1 ng P-CTXs g-1 fish daily. Over a 30 d exposure, P-CTX-1, -2, and -3 were consistently detected in various tissues of exposed fish, and the concentrations of the total P-CTXs in tissues generally ranked following the order of liver, intestine, gill, skin, brain, and muscle. Relatively higher uptake rates of P-CTX-1 in the groupers were observed compared with those of P-CTX-2 and -3. The depuration rate constants of P-CTX-1, -2, and -3 in different tissues were (0.996-16.5) × 10-2, (1.51-16.1) × 10-2, and (0.557-10.6) × 10-2 d-1, respectively. The accumulation efficiencies of P-CTX-1, -2, and -3 in whole groupers were 6.13%, 2.61%, and 1.15%, respectively. The increasing proportion of P-CTX-1 and the decreasing proportion of P-CTX-2 and -3 over the exposure phase suggest a likely biotransformation of P-CTX-2 and -3 to P-CTX-1, leading to higher levels of P-CTX-1 in fish and possibly a higher risk of CTXs in long-term exposed fish.