Calcium acting through the ionophore A-23187 caused massive K(+) release from rat parotid slices. The ionophore thus simulates the action of epinephrine on the alpha-adrenergic receptor in this system. The alpha-adrenergic and cholinergic receptors are, however, not involved in the action of the ionophore since phetolamine and atropine had no effect on the ionophore-induced K(+) release. Amylase secretion, which is induced by epinephrine through the beta-adrenergic receptor but does not require Ca(++) in the medium, was only slightly increased by the ionophore in the presence of Ca(++). The K(+) released by Ca(++) through the ionophore was regained by the cells upon chelation of Ca(++) with ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid. Similar to the action of epinephrine on the alpha-adrenergic receptor, the K(+) release induced by the ionophore is specific for Ca(++), which cannot be substituted by 2.5 mM Sr(++), Mg(++), or Ba(++). The results suggest that epinephrine, like the ionophore, introduces Ca(++) into the cell to mediate K(+) release. It is proposed that the ionophore A-23187 may be an effective probe to test whether other Ca(++)-requiring hormones and neurotransmitters act in a similar fashion to produce their diverse physiological responses.