Agonist stimulation of human pulmonary artery smooth muscle (PASMC) and endothelial (PAEC) cells with histamine showed similar spatiotemporal patterns of Ca²⁺ release. Both sustained elevation and oscillatory patterns of changes in cytosolic Ca²⁺ concentration ([Ca²⁺]_cyt) were observed in the absence of extracellular Ca²⁺. Capacitative Ca²⁺ entry (CCE) was induced in PASMC and PAEC by passive depletion of intracellular Ca²⁺ stores with 10-µM cyclopiazonic acid (CPA, for 15-30 min). The pyrazole derivative BTP2 inhibited the CPA-activated Ca²⁺ influx, suggesting that depletion of CPA-sensitive internal stores is sufficient to induce CCE in both PASMC and PAEC. The recourse of histamine-mediated Ca²⁺ release was examined after exposure of the cells to CPA, thapsigargin, caffeine, ryanodine, FCCP, or bafilomycin. In PASMC bathed in Ca²⁺-free solution, treatment with CPA almost abolished histamine-induced rises in [Ca²⁺]_cyt. In PAEC bathed in Ca²⁺-free solution, however, treatment with CPA eliminated the histamine-induced sustained and oscillatory rises in [Ca²⁺]_cyt, but did not affect the initial transient increase in [Ca²⁺]_cyt. Furthermore, treatment of PAEC with a combination of CPA (or thapsigargin) and caffeine (and ryanodine), FCCP, or bafilomycin did not abolish the histamine-induced transient [Ca²⁺]_cyt increases. These observations indicate that a) depletion of CPA-sensitive stores is sufficient to cause CCE in both PASMC and PAEC; b) induction of CCE in PAEC does not require depletion of all internal Ca²⁺ stores; c) the histamine-releasable internal stores in PASMC are mainly CPA-sensitive stores; d) PAEC, in addition to a functional pool that is sensitive to CPA, contain other stores that are insensitive to CPA, thapsigargin, caffeine, ryanodine, FCCP, and bafilomycin; and e) the CPA-insensitive stores in PAEC, while may not contribute to CCE, contribute to histamine-mediated Ca²⁺ release.