Normal serums are most commonly used for blocking to reduce background staining in immunohistochemistry. Blocking with normal serum from the same species that your secondary antibody was raised in can significantly reduce background when doing immunohistochemistry, immunocytochemistry, or any immunoassay. For example, if your primary antibody was raised in rabbit, then you might use a goat anti-rabbit secondary antibody. In this case, you would use normal goat serum in the first blocking step, before application of your primary antibody. This helps bind up any nonspecific or reactive binding sites. This first incubation with the normal serum should be performed from one hour to overnight, at room temperature to 4 degrees. After this, the primary antibody should be applied. You never want to block with a blocking serum which is the same species that your primary antibody was raised in as this would actually increase background. In our above example, the primary antibody is raised in rabbit, so you would never want to use normal rabbit serum. If you used normal rabbit serum, immunoglobulins present in the normal serum would bind to nonspecific reactive sites, which would then bind your secondary antibody and create nonspecific background signal. If used correctly, blocking with normal serums can increase the sensitivity of your immunoassay, as well as improving the signal to noise ratio.