The spleen is the largest secondary lymphoid organ, is considered the draining site for compounds that are administered intravenously, and is therefore considered an important organ to evaluate for treatment-related lesions. Due to the presence of B and T lymphocytes, the immunotoxic effects of xenobiotics or their metabolites on these cell populations may be reflected in the spleen. Therefore it is one of the recommended organs to evaluate for enhanced histopathology of the immune system. The two major functional zones of the spleen are the hematogenous red pulp and the lymphoid white pulp (periarteriolar sheaths, follicles and marginal zones). For enhanced histopathology, these splenic compartments should be evaluated separately for changes in size and cellularity, and descriptive rather than interpretive terminology should be used to characterize any changes (Haley et al., 2005). Moreover, germinal center development within the lymphoid follicles should be noted as increased or decreased.