Although there are many applications of silver nanoparticles (Ag-NPs) in human activities,there is still little known about their potential environmental toxicity, particularly to fish. Inthe present study, the effects of Ag-NPs on African catfish (Clarias gariepinus) were studiedusing melanomacrophage centers as immunohistological biomarkers. Fish were exposed to25 mg/L, 50 mg/L and 75 mg/L 100-nm Ag-NPs. We studied the effects on the size and num-ber of melanomacrophage centers in all target tissues. Many histopathological alterationsin those tissues were observed. The histological changes were represented as dislocationof the epithelium, dilatation of central veins associated with inflammatory leukocytic infil-tration, necrosis, and pyknotic nuclei of hepatocytes. There was shrinkage of Malpighiancorpuscles, dislocation of nuclei of convoluted tubules, cellular degeneration, and dispersedinfiltration of leukocytes in kidney tissue. Examination of spleen sections after exposure toAg-NPs showed rupture within the red pulp and hemorrhage, dislocation of nuclei, accumu-lation of inflammatory leukocytes, and congestion in blood vessels. In conclusion, exposureto Ag-NPs induced alterations in tissues, suggesting a possible increase in oxidative stressin those tissues.