Human biopsy (30), surgical (50) and autopsy (14) specimens of different embryonic origin (skin, blood vessel, kidney, lymph nodes, prostate, lung, liver, and intestine) were stained by the avidin-biotin complex immunoperoxidase technique (ABC-IP) with monoclonal antibodies (MAbs). MAb T2G1 (recognizes 315-42 and detects fibrin II in tissues), MAb I8C6 (recognizes BS1-42 and indicates fibrinogen and fibrin I), MAb GC4 (specific for fragments D and D-D), and a polyclonal antiserum for fibrinogen. The method can be applied to frozen or Boilin’s fixed paraffin embedded tissues with good preservation of morphology and high sensitivity at the light microscopy level. The results were compared with conventional histochemical stains currently used in surgical pathology to demonstrate fibrin deposits in tissues. These stains are based on the acidophilic properties of fibrin (Fraser-Lendrum for “more recent” and Mallory’s PTAH for “older” fibrin). ABC-IP staining with MAb T2G1 clearly detected fibrin in areas where Lendrum and PTAH failed to reveal fibrin deposits, e.g., in the intercellular and pericellular matrix, as well as in areas where staining occurred with conventional techniques, indicating greater sensitivity of the ABC-IP method. Fibrin was specifically detected in strands or clumps in some areas of inflammation and granulation tissue and seemed to be associated with platelets and macrophages. Moreover, ABC-IP with MAb I8C6 and MAb GC4 permits the distinction between fibrinogen or fibrin I, and D and D dimer which are poorly reactive with the Lendrum and PTAH methods. The polyclonal antiserum for fibrinogen showed reactivity with all the material stained with the MAbs and with some additional areas due to the epitopes of fibrinogen and fibrin not detected by the monoclonals. The ABC-IP technique with MAbs allows specific demonstration of fibrin deposits in tissues. Moreover, these results indicate that this method facilitates the correlation of the morphologic appearance of fibrinogen) -related deposits in tissues with their molecular form and will be useful to elucidate the role of fibrin in diseases such as atherosclerosis, kidney disease, and tumors.