The present study compares the rates of Ca²⁺ uptake and Cd²⁺ accumulation in tilapia (Oreochromis mossambicus) between larvae preexposed to Cd²⁺ and naive larvae. Preexposure to Cd²⁺ induces some form of adaptation that attenuates the effects of Cd²⁺ later on. Exposure to Cd²⁺ decreased the uptake of Ca²⁺ but did not suppress the accumulation rate of Cd²⁺. A 12-fold increase in 96-h half-maximal lethal concentration was found in tilapia larvae preexposed to 0.45 µM Cd²⁺ from hatching for 3 days in comparison with naive 3-day-old larvae. The effects of Cd²⁺ on Ca²⁺ influx kinetics in larvae preexposed to 0.18 µM Cd²⁺ for 3 days were examined. The Michaelis constant for Ca²⁺ in the 0.18 µM Cd²⁺ preexposed larvae did not change significantly in the presence of Cd²⁺, whereas maximal velocity increased by ~23%. An enhanced Ca²⁺ uptake efficiency (~18%) was found in these Cd²⁺-acclimated larvae. The criterion that determines the survival of tilapia larvae encountering Cd²⁺ challenge is the degree of interference with Ca²⁺ homeostasis instead of the absolute amount of Cd²⁺ accumulated.