Specimens of human fibrinogen mixed with Fab fragments of antibodies that were specific for various portions of the fibrinogen molecule were tungsten shadow-cast and examined by electron microscopy. Typical trinodular fibrinogen molecules were observed when Fab fragments were omitted or when fragments from nonimmune sera were used. In the experimental fibrinogen-Fab preparations, a significant number of molecules were found with an extra nodule. In the case of Fab fragments from antibodies directed to fragment E, the additional nodule was attached to the central sphere of the fibrinogen molecule. Simi A in length. The model they developed on the basis oftheir micrographs consisted oftwo terminal spheres, each about 60 A in diameter, connected to a slightly smaller central sphere, the diameter ofwhich was estimated to be 50 A. The connections between the spheres were unresolvable and were assumed to be rods less than 15 A thick. In the ensuing period, electron microscopy changed rapidly, and shadow-casting procedures gave rise to negative-staining techniques. The latter led to a number ofreports indicatingthat fibrinogen was not a trinodular rod but was in fact-a large bloated or hollow ball (2-4). Indeed, the physicochemical properties of the molecule could be interpreted in different ways; primarily because of the difficulty in distinguishing asymmetry from hydration, and either of these extreme models could be accommodated satisfactorily. Subsequently, a series ofreports appeared that purported to show that the trinodular structure ofHall and Slayter was an artifact ofthe procedure used (5, 6).On the other hand, a considerable amount of biochemical support for the Hall and Slayter model has accumulated over the years, beginning withthe nature ofthe core fragments produced by limited proteolysis (7,8) and continuing with the actual kinetics of generation of those fragments, which included asymmetric intermediates of the sort that would be expected fromThe publication costs ofthis article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.cleavages between the spheres (9). A number of other experiments also provided additional, although less direct, support for a triglobular model (10-13).Recently, shadow-casting procedures have been revived for the study of fibrinogen, and once again trinodular structures of the sort shown by Hall and Slayter have been viewed (14,15). Furthermore, Fowler and Erickson (15) were even able to show a trinodular structure by negative-staining techniques, and Estis and Haschemeyer (16) observed a similar structure in unstained preparations. Moreover, a plethora of detailed biochemical data exist, all of which, including the complete amino acid sequence of the molecule and the exact arrangement of disulfide bonds that bridge the six subunit chains (17)(18)(19)(20)(21)(22), are consistent with the Hall and Slayter model. The picture that has emerged is a po...