There is growing interest and concern in society about the capacity of chemicals to impair immune responses and trigger autoimmune disease. Methods to investigate chemical-induced immunosuppression have been developed and validated in the mouse and rat. Animal models that are suitable to investigate the ability of chemicals to induce autoimmune disease are virtually lacking. From the plethora of tests to assess immunity in man, panels of biomarkers to study immunotoxicity in humans have been proposed. Such studies in humans are considerably more complex than in animals as non-invasive tests are limited, responses in the population are heterogeneous, and exposure levels are often low. Human risk assessment is therefore mostly based on animal studies. As examples of compounds affecting biomarkers in animals and man, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and hexachlorobenzene are discussed.