A complement inhibitor (CI) has been isolated from cobra (Naja haje) venom which is distinct from the two known anticomplementary factors in cobra venom [1], in functional properties as well as structure. CI is a small (mol. wt 26,000, determined by sodium dodecyl sulphate gel electrophoresis), heat-labile glycoprotein; the amino acid composition is that of a globular protein. CI interferes at various steps of the complement sequence, including reactions of the classical and alternative pathway. No effect was observed on C4 fixation and on the assembly of the membrane attack complex from C6-9 (minor inhibiting effects, if present, have not been excluded). Initiation of the alternative pathway is inhibited by CI already at the stage of cleavage of factor B. CI binds to C4, C4b, C3 and C3b; since the major inhibitory action of CI is lost after washing of cell intermediates, complex formation and, as a consequence, steric hindrance may be responsible for the inhibiting effects of CI. CI also interferes with binding of C3b to C3b receptors on human erythrocytes. CI is non-toxic in mice when given intraperitoneally in doses of 5 microgram/g.