When Sr2+ was introduced to the external solution after the depletion of Ca2+ from stores of submandibular acinar cells by ACh stimulation, Sr2+ entered cytoplasm of the cell, like the case of Ca2+. SK&F 96365, a Ca2+ channel blocker, or Ni2+ blocked this divalent cation entry. Sr2+ entering the cell continued to increase to a steady level, after the cessation of stimulation, when Sr2+ was present in the external solution, unlike the case of Ca2+. Ca2+ entered cells which had been stimulated with ACh in Sr(2+)-containing external solution. In the cells to which Sr2+ has been applied after the store depletion with ACh, Sr2+ cannot be released by the renewed ACh stimulation, unlike the case of Ca2+. 89Sr2+ uptake by the parotidic microsomal fraction 100 min after addition of ATP was 15.08 +/- 0.70 nmol/mg protein, whereas 45Ca2+ uptake was 144.19 +/- 16.93 nmol/mg protein. It was concluded that in the salivary acinar cells Sr2+ can be a substituent for Ca2+ in the mechanism of entry from the extracellular fluid but cannot be in the mechanism of uptake into the stores.