Thapsigargin (Tg), a microsomal Ca²⁺pump inhibitor, dose-dependently increases the cytoplasmic Ca²⁺concentration and aldosterone production without having any striking effect on the formation of inositol phosphates in isolated rat adrenal glomerulosa cells. The interaction of Tg with the major Ca²⁺-mediated stimuli of glomerulosa cells on aldosterone production was also exam-ined. The effects of Tg and the Ca²⁺-mobilizing angiotensin-II (AII) were additive. The aldosterone production stimulatory effect of potassium, which induces Ca²⁺influx via voltage-operated Ca²⁺channels, was potentiated by Tg. The positive interaction between Tg and potassium on aldosterone production raises the possibility that stimuli generating Ca²⁺signal by depleting intracellular Ca²⁺stores, such as Tg or AII, enhance the response of the cell to depolarization. Such an interaction between AII and potassium may have an important role in the physiological control of aldosterone production.