A euglobulin fraction of human C'1 has been chromatographically resolved into three distinct activities, designated C'1q, C'1r, and C'1s, in the order of their elution from DEAE cellulose. All three of these activities have been shown to participate in various hemolytic reactions requiring C'1, including the cold phase of the Donath-Landsteiner reaction, and to be necessary for generation of C'1 esterase. C'1q was identical with a previously described serum protein implicated in a very early step of complement action and designated the 11S component on the basis of its sedimentation constant. C'1r could not be related to a known complement activity and has been presented as a new component. C'1s, on the basis of chromatographic evidence, was identified with C'1 proesterase. Methods of assay of these components of C'1 have been presented.

The significance of C'1q, C'1r, and C'1s in generation of C'1 esterase and the central role of this enzyme in reactions involving C'1, C'4, and C'2 have been discussed.

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