There is increasing evidence that chronic, subclinical exposure to certain environmental pollutants may upset immune responsiveness and alter susceptibility of animals to infectious agents. Environmental chemicals or drugs may affect diverse aspects of the immune system, leading to immunosuppression, immunopotentiation, hypersensitivity or perturbed innate host resistance. A variety of infectious models is available that involves relatively well defined target organs and host defense mechanisms; for example, infections with encephalomyocarditis virus, Herpesvirus simplex, Listeria monocytogenes, Streptococcus pneumoniae, Escherichia coli or Plasmodium berghei. Important variables in infectious models used to assess immunotoxicity include species and strain of animal used, their age and sex, the route of exposure, and dose of the chemical. No one infectious model has yet emerged as a routine screening tool to detect and assess the subtle effects that may occur in immune responses when animals are exposed to doses of environmental pollutants that cause no adverse effect at a gross level. The selection of useful test systems is complicated because it is difficult to measure the effects of chronic, subclinical exposure to chemicals and sublethal challenges of microorganisms.