BACKGROUND: Many biological and chemical agents have the capacity to alter the way the immune system functions in human and animals. This study evaluates the immunotoxicity of 20 substances used widely in work environments. METHODS: A systematic literature search on the immunotoxicity of 20 chemicals was performed. The first step was to review literature on immunotoxicity testing and testing schemes adopted for establishing immunotoxicity in humans. The second step consisted of providing a documentation on immunotoxicity of substances that are widely used in work environment, by building tables for each chemical of interest (benzene, trichloroethylene, PAHs, crystalline silica, diesel exhausts, welding fumes, asbestos, styrene, formaldehyde, toluene, vinyl chloride monomer, tetrachloroethylene, chlorophenols, 1,3-butadiene, mineral oils, P-dichlorobenzene, dichloromethane, xylene, 1,1,1-trichloroethane, ethylene oxide). The third step was the classification of substances; an index (strong, intermediate, weak, nil) was assigned on the basis of the evidence of toxicity and type of immunotoxic effects (immunosuppression, autoimmunity, hypersensitivity) on the basis of the immune responses. Finally substances were assigned a score of immunotoxic power. RESULTS: Tables have been produced that include information for the 20 substances of interest, based on 227 animal studies and 94 human studies. Each substance was assigned an index of immunotoxic evidence, a score of immunotoxic power and type of immunotoxic effect. CONCLUSIONS: This matrix can represent a tool to identify chemicals with similar properties concerning the toxicity for the immune system, and to interpret epidemiological studies on immune-related diseases. Am. J. Ind. Med. 2006. (c) 2006 Wiley-Liss, Inc.