The enrichment in phosphatidylinositol 4-phosphate and phosphatidylinositol 4-5-bisphosphate of cardiac sarcolemmal vesicles stimulate Na+/Ca2+ exchange activity. On the contrary the deacylation products of polyphosphoinositides are powerful inhibitors of Na+/Ca2+ exchange: half maximal inhibition of 1.6 and 2.1 microM have been observed for glycerophosphoinositol 4-phosphate and glycerophosphoinositol 4-5-bisphosphate, respectively. The data indicate a bidirectional regulation of Na+/Ca2+ exchanger and suggest that phosphorylated glycerophosphoinositols can be regarded as novel signal transducers of intracellular Ca2+ regulation in heart cell.