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1. The uptake and loss of Mn has been studied in perfused isolated frog ventricles, at rest, during activity, in Na-free fluid and in K-rich fluid. 2. In normal Ringer the uptake of Mn with time is composed of two phases which can be interpreted as an initial saturating phase and a slower non-saturating phase. The uptake in the resting heart is estimated to be 1.91 X 10(-14) M.cm-2.sec-1, and the extra uptake associated with the action potential to be 6.90 X 10(-13) M.cm-2.beat-1, when the heart is exposed to Ringer containing 8 mM-Mn. 3. The washout of Mn from preloaded ventricles into Mn-free Ringer is composed of at least two exponential phases. The slowest phase corresponding to a rate of Mn efflux of 1.72 X 10(-14) M.cm-2.sec-1. 4. Mn uptake is not increased by exposure of the muscle to Na-free fluids but is markedly increased by exposure to depolarizing fluids. 5. The Mn accumulating in the ventricles during a 7 1/2 min exposure to 8 mM-Mn-ringer with an elevated [K], increases with increasing [K]o to reach a peak at 75 mM-K and then falls to quite a low value in 120 mM-K. 6. The results are discussed in the light of the action of Mn ions on the contraction and the ionic currents of frog heart muscle.

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