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1. External application of 10(-4) M digitoxigenin caused an 80% fall in the Na efflux in barnacle muscle fibres. The observed inhibition was irreversible and could be produced by as little as 10(-7) M digitoxigenin. 2. Internal application of 10(-2) M digitoxigenin lowered the Na efflux by 46% but was without effect following addition of external ouabain or K removal. 3. External application of digitoxigenin (or ouabain) following internal application of the aglycone was without effect on the Na efflux. 4. The efflux of [3H]digitoxigenin was fairly rapid, whereas that of [3H]ouabain was slow. 5. Inhibition of the Na efflux by internal application of digitoxigenin is probably the result of an action of the aglycone on the external side of the membrane following its leakage from the fibre interior.