This paper presents a toxicokinetic/toxicodynamic analysis to appraise arsenic (As) bioaccumulation in farmed juvenile milkfish Chanos chanos at blackfoot disease (BFD)-endemic area in Taiwan, whereas probabilistic incremental lifetime cancer risk (ILCR) and hazard quotient (HQ) models are also employed to assess the range of exposures for the fishers and non-fishers who eat the contaminated fish. We conducted a 7-day exposure experiment to obtain toxicokinetic parameters, whereas a simple critical body burden toxicity model was verified with LC50(t) data obtained from a 7-day acute toxicity bioassay. Acute toxicity bioassay indicates that 96-h LC50 for juvenile milkfish exposed to As is 7.29 (95% CI: 3.10-10.47) mg l(-1). Our risk analysis for milkfish reared in BFD-endemic area indicates a low likelihood that survival is being affected by waterborne As. Human risk analysis demonstrates that 90%-tile probability exposure ILCRs for fishers in BFD-endemic area have orders of magnitude of 10(-3), indicating a high potential carcinogenic risk, whereas there is no significant cancer risk for non-fishers (ILCRs around 10(-5)). All predicted 90%-tiles of HQ are less than 1 for non-fishers, yet larger than 10 for fishers which indicate larger contributions from farmed milkfish consumptions. Sensitivity analysis indicates that to increase the accuracy of the results, efforts should focus on a better definition of probability distributions for milkfish daily consumption rate and As level in milkfish. Here we show that theoretical human health risks for consuming As-contaminated milkfish in the BFD-endemic area are alarming under a conservative condition based on a probabilistic risk assessment model.