The effects of the WT on store-mediated Ca2+ entry and protein tyrosine phosphorylation were investigated in fura-2-loaded human platelets. Wortmannin (2 μM) attenuated the rise in [Ca2+]i caused by Ca2+ entry while having no effect on the mobilisation of Ca2+ from internal stores. It also reduced store-depletion-evoked protein tyrosine phosphorylation. These findings demonstrate that WT is an inhibitor of tyrosine phosphorylation and store-mediated calcium entry and provide further evidence for the involvement of a tyrosine phosphorylation step in the link between Ca2+ store depletion and Ca2+ influx in human platelets.