Eicosapentaenoic acid (EPA) caused elevations of intracellular free Ca2+ concentration ([Ca2+]i) measured by fura-2 fluorescence in cultured human endothelial cells. The EPA-induced increase in [Ca2+]i could still be observed when either cyclooxygenase or lipoxygenase inhibitors were added. These results suggest that EPA itself rather than its metabolites has direct effects on intracellular Ca2+ mobilization, causing the elevation of [Ca2+]i.