The first component of complement, C1, is a calcium-dependent complex of two loosely interacting subunits: C1q, responsible for the binding of activators to C1; C1r2-C1s2, which supports the autoactivation potential of C1, together with the proteolytic activity of activated C1- on its two substrates, C4 and C2. Isolated dimeric C1r2 is able to autoactivate through an intradimer cross-proteolysis; this capacity is lost when C1r2 is associated with two molecules of C1s inside the calcium-dependent C1r2-C1s2 subunit; this capacity is again observed in reconstituted C1. A model for reconstituted soluble C1 is proposed, based on electron microscopy, neutron diffraction, ultra-centrifugation, various biochemical findings, as well as functional properties of C1 or of its subcomponents. The flexible rod-like structure of C1r2-C1s2 is folded around two arms of C1q, with the catalytic domains of C1r and C1s inserted inside the cone defined by the C1q stalks. Activation of C1 which, in vivo, is controlled by C1 inhibitor, can be achieved by various activators, such as immune complexes; it appears to result from the suppression of a negative control and resides in a positive modulation of the intrinsic autocatalytic potential of C1r inside C1.