Cells of the immune system are found in every organ, from the classic lymphoid organs to tissues such as liver, mucosae, and omental adipose tissue. Toxicity to the immune system may be from a direct or indirect injury to lymphoid organs. The morphological responses range from lymphocyte depletion to proliferation, and may result in an increased susceptibility to infections and in the development of tumors. Toxicity may also be caused via the generation of a specific immune response against the compound or by deregulation of immunological responses, leading to allergy/hypersensitivity or autoimmune disease. The damage can be found at multiple sites of the body, depending on the specificity of the hypersensitivity or autoimmune response. Special attention is needed to evaluate toxicity to the immune system in sensitive groups; response may be modified by age, pregnancy, genetic make-up, and compromising conditions like metabolic syndrome and asthma. © 2013 Copyright © 2013 Elsevier Inc. All rights reserved.