The activation of the complement component C3 generates C3a and C3b fragments, and the physiological cleavage of C3b further yields C3c and C3d fragments. We studied here by enzyme immunoassay the ability of human plasma fibronectin to interact with native C3 of human sera and with isolated C3c and C3d fragments of C3. C3 from sera of all six individuals tested bound to solid-phase fibronectin. Soluble fibronectin bound to solid-phase C3c and C3d, and fluid-phase C3c and C3d also bound to solid-phase fibronectin. The binding of fibronectin to solid-phase C3c and C3d could be inhibited by fluid-phase C3c and C3d. The results suggest the possibility that soluble fibronectin may attach to C3-coated particles or that C3-coated particles may adhere to fibronectin-containing structures.