The mechanisms via which t-PA release is mediated are incompletely understood. Bradykinin, an endogenous endothelium-dependent vasodilator, causes the endothelial release of t-PA. However, Brown et al have demonstrated that inhibition of prostacyclin and nitric oxide synthesis does not diminish bradykinin mediated endothelial t-PA release in the human forearm. Therefore, they suggest that EDHF is responsible for the endothelial release of t-PA but, to date, this hypothesis has not been adequately addressed.