Fibrinogen participates in important cellular physiological processes, such as cell adhesion and blood clotting. Although the primary and secondary structures of fibrinogen are known, its tertiary structure is yet to be determined. In attempts to understand the tertiary structure of this important hydrated cellular and plasma membrane protein, the present study using atomic force microscopy was carried out. The techniques presented in this manuscript may also be applicable to enhance the imaging of live cells as well as their subcellular components. The authors have imaged fibrinogen by Tapping Mode atomic force microscopy in fluid. Purified human fibrinogen, together with 15-nm colloidal gold particles serving as an internal calibration standard, were adhered to a poly-L-lysine substrate on freshly cleaved mica. Atomic force microscopy images were obtained using oxide-sharpened silicon nitride probes, either unaltered or with an electron beam deposited extended tip. Although various structures were observed, the predominant forms consisted of a bi- or trinodular slightly curved linear shape. Approximately 300 of these structures were observed with six different tips (1 unaltered and 5 electron beam deposited) and their lengths and heights were analyzed. The mean length of the fibrinogen molecules was 65.8 nm and the mean height was 3.4 nm. The quantitative measurements were little influenced by the shape of the tip, whereas the sharper electron beam deposited tips seemed to produce qualitatively superior images.