The mechanism of amylase and sialic acid releases stimulated by pilocarpine or high K+ medium was investigated in the slices of dog submandibular glands. The release of both amylase and sialic acid was dose-dependently increased by pilocarpine and a considerable release was observed at pilocarpine concentrations of more than 1 /tM. Similar effects were observed when K+ concentration in the medium was increased and the maximal response was observed at 75 mM K+. The release of amylase and sialic acid by pilocarpine or K+ considerably decreased by removing Ca2+ from the medium and the slices. The release of amylase in the Ca2 + -deficient slices was nearly recovered by the addition of 2.5 and 5.0 mM Ca2+, whereas that of sialic acid was recovered by only 60-75 %. Ca2+ inhibitors, La3+ and verapamil, and calmodulin inhibitors, trifluoperazine, prenylamine, and W-7, significantly inhibited the release of amylase and sialic acid induced by the stimulants. These results suggest that the release of amylase and sialic acid stimulated by pilocarpine or K+ is dependent on the presence of Ca2+, and that the activation of calmodulin is involved in the process of the release.