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1. Dispersed rat parotid acinar cells were used to study the effects of secretagogues on 22Na uptake. 2. Carbachol stimulated 22Na uptake, and caused a net gain in total Na and a loss in total K. These effects were accentuated in the presence of 10(-3) M-ouabain. 3. Substance P, epinephrine and phenylephrine also stimulated 22Na uptake while isoproterenol and angiotensin II did not. 4. The 22Na uptake due to carbachol was inhibited by atropine, procaine or CoCl2; the response to Substance P was inhibited by CoCl2 only. 5. Extracellular Ca was required for stimulation of 22Na uptake by carbachol. Strontium but not Ba could substitute for Ca in supporting 22Na uptake. 6. Uptake of 22Na was stimulated by the divalent cationophore, A-23187, and Ca was required for this effect. 7. It is concluded that activation of Ca influx by muscarinic, alpha-adrenergic or peptide agonists triggers, among other effects, an increased membrane permeability to Na.