Coordination of intercellular Ca²⁺ signals is important for certain hepatic functions including biliary flow and glucose output. Prostaglandins, such as PGF2 and PGE2 may modify these hepatocyte functions by inducing Ca²⁺ increase, but very little is known about the organization of the Ca²⁺ signals induced by these agonists. We studied Ca²⁺ signals induced by PGF2 and PGE2 in Fura2-AM-loaded hepatocyte doublets. Even though both prostaglandins induced Ca²⁺ oscillations, neither PGF2 nor PGE2 induced coordinated Ca²⁺ oscillations in hepatocyte doublets. Gap junction permeability (GJP), assessed by fluorescence recovery after photobleaching, showed that this absence of coordination was not related to a defect in GJP. InsP₃ assays and the increase in InsP₃ receptor sensitivity to InsP₃ observed in response to thimerosal suggested that the absence of coordination was a consequence of the very small quantity of InsP₃ formed by these prostaglandins. Furthermore, when PGE2 and PGF2 were added just before noradrenaline, they favored the coordination of Ca²⁺ signals induced by noradrenaline. However, GJP between hepatocyte doublets was strongly inhibited by prolonged (2 h) treatment with PGF2, thereby preventing the coordination of calcium oscillations induced by noradrenaline in these cells. Thus, depending on the time window, prostaglandins, specially PGF2, may enhance or diminish the propagation of Ca²⁺ signals. They may therefore contribute to the fine tuning of Ca²⁺ wave-dependent functions, such as nerve stimulation, hormonal regulation of liver metabolism or bile secretion, in both normal and pathogenic conditions.