Abstract The purpose of this study was to elucidate the mechanism by which bradykinin (BK) enhances prostacyclin (PGI 2) production in human umbilical vein endothelial cells (HUVEC). BK-induced enhancement of PGI 2 synthesis was observed in a dose- and time-dependent manner, and it also increased [Ca 2+] i followed by enhancement of cytosolic phospholipase A 2 (cPLA 2) activity. The PKC inhibitors GF109203X and H7 attenuated the BK-induced increase in [Ca 2+] i and inhibited the BK-induced PGI 2 synthesis. Phorbol 12-myristate 13-acetate increased cPLA 2 activity and PGI 2 synthesis but failed to alter [Ca 2+] i. BK increased cPLA 2 mRNA eightfold by 15 min, and this increase was inhibited by pretreatment with the PKC inhibitors. In response to cycloheximide pretreatment, cPLA 2 mRNA was superinduced. These results suggest that BK stimulates PGI 2 synthesis in HUVEC by activation of cPLA 2 by dual mechanisms: an elevation of [Ca 2+] i and a PKC-dependent pathway. Moreover, changes in calcium kinetics and expression of cPLA 2 mRNA may underlie the BK-induced PGI 2 enhancement in these cells.