The relationships among the uptake of toxic methylmercury (MeHg) and two important fish physiological processes-respiration and water pumping--in the Nile tilapia (Oreochromis niloticus) were explored in the present study. Coupled radiotracer and respirometric techniques were applied to measure simultaneously the uptake rates of MeHg, water, and oxygen under various environmental conditions (temperature, dissolved oxygen level, and water flow). A higher temperature enhanced MeHg influx and the oxygen consumption rate but had no effect on the water uptake, indicating the influence of metabolism on MeHg uptake. The fish showed a high tolerance to hypoxia, and the oxygen consumption rate was not affected until the dissolved oxygen concentration decreased to extremely low levels (below 1 mg/L). The MeHg and water uptake rates increased simultaneously as the dissolved oxygen level decreased, suggesting the coupling of water flux and MeHg uptake. The influence of fish swimming performance on MeHg uptake was also investigated for the first time. Rapidly swimming fish showed significantly higher uptake rates of MeHg, water, and oxygen, confirming the coupling relationships among respiration, water pumping, and metal uptake. Moreover, these results support that MeHg uptake is a rate-limiting process involving energy. Our study demonstrates the importance of physiological processes in understanding mercury bioaccumulation in fluctuating aquatic environments. Copyright © 2011 SETAC.