Interest has blossomed in the development of complement inhibitors, in para
llel with a growth in our understanding of the biology of the complement ca
scade. The first generation of designed inhibitors was based on naturally o
ccurring complement receptors and regulatory molecules. These agents provid
ed useful tools for exploring the role of complement in experimental models
of disease, but may have limited therapeutic application in humans because
of their short half-lives, limited bioavailability and possible antigenici
ty, More recently, humanized antibodies and synthetic molecules that block
the activation of complement have been developed, which look as though they
may overcome some of these difficulties, The possibility for precision inh
ibition of a limited part of the complement cascade, or for inhibition conf
ined to a single organ, may offer effective therapeutic results, while avoi
ding the disadvantages of nonselective complement blockade. This review exa
mines the recent evidence that complement inhibition will reduce tissue dam
age resulting from organ transplantation, ischaemia-reperfusion injury, can
cer, glomerulonephritis and the use of extracorporeal circuits. Curr Opin N
ephrol Hypertens 8:557-562. (C) 1999 Lippincott Williams & Wilkins.