Specific receptors for fibrinogen can be induced on platelets by a variety of stimuli. In this study, two independent approaches have implicated the D domain of fibrinogen in its interaction with the platelet. Immunochemically purified Fab fragments of anti-fibrinogen and anti-D inhibited 125I-fibrinogen binding to platelets in a dose-dependent fashion and platelet aggregation. In contrast, Fab fragments of anti-E produced only a slight inhibition of fibrinogen binding and nonimmune Fab fragments had no effect. Fibrinogen was digested with plasmin in the presence of 5 mM calcium and fragment D and E of Mr 100,000 and 50,000, respectively, were isolated. This D fragment inhibited 125I-fibrinogen binding to platelets in a concentration-dependent fashion, whereas the E fragment was ineffective. With 125I-fibrinogen at 0.17 microM, nonlabeled fibrinogen inhibited binding by 50% at 0.7 microM, whereas 170 microM fragment D was required to produce 50% inhibition. D fragment of Mr 80,000, generated in the absence of calcium, was noninhibitory. These observations provide strong evidence for the participation of the D domain in the binding of fibrinogen by its platelet receptor and suggest that the recognition site is lost in the conversion of the Mr 100,000 to 80,000 D species.