Purified CĪs, subcomponent of CĪ, induced electrophoretic conversion of factor B and consumption of hemolytic C3 and C5 in sera genetically deficient in C2 or C4. Blocking of the hemolytic activity of CĪs in C2-deficient serum by F(ab′)2 anti-CĪs resulted in inhibition of the alternative pathway, as indicated by the failure of zymosan or cobra venom factor to induce consumption of C3 and C6. Zymosan also failed to activate the alternative pathway when CĪs was absorbed from C1r-deficient serum using a solid immunoabsorbent. These data, showing that CĪs participates in the alternative pathway under certain experimental conditions, suggest the interesting possibility that CĪs is important in the activation sequence of both the classical and the alternative pathway more generally.