We appraised organ-specific toxicokinetics and dose responses of arsenic burdens in tilapia Oreochromis mossambicus. We kinetically linked an Area-under-the-curve (AUC)-based acute toxicity model and a pharmacodynamic model to derive dose-response relationships between equilibrium organ-specific arsenic concentrations and mortality effects. The AUC-based acute toxicity model was also used to derive organ-specific internal effect concentration (IEC)-time-response relationships, which can also be applied to predict a time-mortality profile. We conducted a 7-day exposure experiment to obtain toxicokinetic parameters, whereas the AUC-based acute toxicity model was verified with LC50(t) data obtained from a 7-day acute toxicity bioassay. Our results demonstrated that 96-hour LC50 and incipient LC50 for tilapia exposed to arsenic are 28.68 (95% confidence interval to 24.92 to 32.44) and 25.55 mg L(-1), respectively. Dose-response relationships followed the Hill equation, which could be expressed as organ-specific bioconcentration factors and incipient LC50. Organ-specific dose-response relationships showed that muscle, gill, and liver have a relatively steep sigmoid dose-response profile in that IEC50 were 26.6, 62.5, and 78.5 microg g(-1) dry wt (dw), respectively. Organ-specific arsenic internal lethal burdens were the highest in the gill and the lowest in the muscle in waterborne-exposed tilapia. The IEC and target-organ concentrations derived in this study can be used in site-specific risk assessment.