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1. Single smooth muscle cells were prepared from the guinea-pig taenia coli and the porcine coronary artery by treatment with collagenase, in order to measure the 45Ca flux with special reference to the effects of external cations. 2. In excess [K]o solution, cell suspensions prepared from both tissues showed an increased 45Ca uptake within 3-5 min. In Na-free solution, the cells prepared from taenia coli, but not from coronary artery showed an increased 45Ca uptake. The Ca uptake of the cells paralleled with the tension increase recorded from tissues of both species. 3. The efflux of 45Ca into Ca-free EGTA containing solution was markedly increased by [Na]o in cells from the taenia coli, but not in cells from the coronary artery. 4. The [Na]o-activated 45Ca efflux from cells of the taenia coli was slightly larger in Ca-free solution than in the Ca-containing (10)-4) M) solution. Depolarization of membranes produced by excess [K]o did not effect the [Na]o-activated 45Ca efflux. 5. Increase in [Na]i by treatment with K-free solution suppressed the [Na]o-activated 45Ca efflux in the taenia coli. Re-addition of [K]o reactivated the [Na]o-activated 45Ca efflux. This re-activation was blocked by ouabain. 6. The efflux of 45Ca was slightly activated by [Ca]o in cells from the taenia coli. This [ca]o-activated 45Ca efflux was larger in Na-free solution than in Na-containing solution, thus suggesting interactions between [Na]o and [Ca]o on the Ca efflux. 7. In cells from the taenia coli, 45Ca efflux could still be observed in nominally Na-and Ca-free solution. This residual 45Ca efflux made a large contribution to the total 45Ca efflux. 8. When 45Ca uptake was measured in Na-free (Tris) solution, the [Na]o-activated, [Ca]o-activated and residual 45Ca effluxes of cells from the taenia coli were accelerated, non-selectively. 9. These results obtained with cells prepared from the guinea-pig taenia coli are comparable to the Ca2+ efflux mechanism seen in the squid axon. However, maintenance of low concentrations of [Ca]i seems to require not only the above three 45Ca efflux mechanisms, but also Ca sequestering mechanisms in the cell.