Monoclonal antibodies (mAb's) have been used extensively in biochemical and biomedical studies, including immunoelectron microscopy. Production of mAb's consists of four steps: immunizing the animal usually a mouse, obtaining immune cells from the spleen of the immunized mouse, fusing the spleen cells with myeloma cells to obtain hybridomas, and selecting the hybridoma cell line producing the desired mAb. In this chapter, we present a general method for monoclonal antibody production.