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.