Abstract: Background :Human fascioliasis is another newly emerging health challenge in Egypt ,up till now and due to many factors, its diagnosis is a problematic issue. In many cases, a considerable damage of the hepatic tissue, often occurs before a proper diagnosis could be done, which in turn necessitates finding a reliable, easily applicable and locally affordable diagnostic test to overcome the diagnostic difficulties that handicap the prevention and control efforts. Subjects & Methods: Stool and serum samples were collected from 35 fascioliasis patients having clinical and parasitological evidences, 20 patients harboring other parasites(Schistosoma mansoni & haematobium, Wuchereria bancrofti and Echinococcus granulosus ) and 25 healthy subjects. A pair of monoclonal antibodies (MAbs), which had been raised against both Fasciola gigantica excretory-secretory (E/S) products and crude Fasciola gigantica antigens, was employed in sandwich ELISA for the detection of E/S antigens in stool specimens (coproantigens) and sera of infected humans. The lower detection limit of coproantigen assay corresponded to 15 ng/ml Fasciola gigantica E/S antigen while that of serum assay corresponded to 50 ng/ml Fasciola gigantica E/S antigen . Results: The anti-Fasciola gigantica MAb- based sandwich ELISA for antigen detection in collected sera showed 77% sensitivity and 100% specificity with 87% diagnostic accuracy, meanwhile, coproantigen detection in stool samples showed 94% sensitivity and 100% specificity with 97% diagnostic accuracy. A positive correlation was detected between antigen level in stool samples and its level in corresponding serum samples. Conclusion: This study showed that the use of anti-Fasciola gigantica MAb- based sandwich ELISA was more sensitive for antigen detection in stool samples of fascioliasis patients than its detection in their corresponding serum samples providing a simple, reliable, non- invasive diagnostic method for active human Fasciola gigantica infection. Key words: human fascioliasis, gigantica,Mabs,diagnosis,ELISA,Egypt