Techniques for the quantification of C3d are shown to estimate the sum of 4 different plasma protein components possessing C3d but not C3c epitopes. All 4 components were C3-derived polypeptides as shown by activating serum containing 125I-labelled C3, isolating the anti-C3d reactive material in 14% PEG supernatant, followed by analysis on SDS-PAGE and autoradiography. Identical results were obtained by radiolabelling 14% PEG plasma supernatants followed by analysis of the anti-C3d reactive material. The components are referred to as d1, d1', d2 and d3 based on their relative electrophoretic mobilities (alpha 1, alpha 1, alpha 2 and alpha 2 respectively) judged by crossed immunoelectrophoresis. Their apparent molecular weights by SDS-PAGE were 129K (d1), 110K (d1'), 46K (d3) and 45K (d2). The possibility that one or more of the C3d containing components represented a complex of a C3 fragment with another plasma protein was investigated. The role of these components in the scheme of the physiological breakdown of C3 and the importance of the individual C3d components as indicators of complement activation in clinical materials is discussed. It is proposed that the 45K d2 component represents a final physiological breakdown product of C3 in human serum.