The peritoneal cavity of guinea pigs proved to be a rich source of mononuclear cells (34-52%) with fibrinogen or fibrin (Fib) on their surface. The Fib was readily detected on the surface of viable cells in suspension by fluorescence microscopy using antisera to guinea pig fibrinogen. The fluorescent staining occurred either in a speckled distribution, similar to that of cytophilic IgG, or in a distinctive net-like pattern that probably represented fibrin formation on the cell surface. The binding of Fib to the cell surface required calcium, but not magnesium, in the medium and could occur in vitro during incubation in heparinized plasma that contained fibrinogen concentrations comparable to that in normal peritoneal fluid (0.58 mg/ml). Cell surface Fib was more susceptible to plasmin and trypsin digestion than surface cytophilic IgG. By morphologic and physiologic criteria, cells exhibiting surface Fib were chiefly, if not exclusively, macrophages. Granulocytes, erythrocytes, and lymphocytes from lymph node and thymus had no sppreciable Fib. Cells with surface Fib were rarely observed among mononuclear cells prepared by Ficoll-Hypaque sedimentation of guinea pig and human blood (1.4 and 4.6%, respectively). Pulmonary alveolar macrophages, functionally distinct from peritoneal macrophages, lacked surface Fib (0.8%). Polymerization of Fib on the surface of macrophages might participate in certain cell interactions, such as the adherence of peritoneal macrophages during the antigen-induced macrophage disappearance reactions. The unexpected finding of Fib binding to the surfaces of peritoneal macrophages raises the possibility of a biologically significant interaction between these cells and the clotting system.