Taken together, with the wide-spread use of ACE-inhibitors within the dialysis population, a novel type of hypersensitivity reaction has been recognized, which may occur not only during hemodialysis but also during other forms of extracorporeal therapy. From the data available today, it seems that such reactions are triggered by negatively charged biomaterials which are capable to activate factor XII, leading among others to the generation of bradykinin. Normally this kinin is rapidly degraded by the serine proteinase kininase II. Thus, in the absence of ACE inhibitors plasma bradykinin levels increase only moderately during dialysis with AN69 membranes and clinically most patients are free of symptoms. However, once kininase II, which is identical with converting enzyme, is blocked by ACE inhibitors, plasma levels may increase more than 100-fold and patients will suffer from severe anaphylaxis. Based on our present knowledge, the consequences for clinical medicine are straightforward. It is mandatory to avoid the combination of negatively charged membranes or other biomaterials with ACE inhibitor therapy. As there are many different membranes available, this should be no unsurmountable problem in the setting of clinical hemodialysis.