Assessing the immunotoxicity of xenobiotics by current regulatory testing has revealed compounds that can cause immunosuppression and stimulation. Flow cytometry is a cutting edge technique that can provide data on how toxicants can alter the quality and quantity of the immune response after exposure. Here we describe protocols for how to use flow cytometry to measure the immune response in multiple rodent organs (blood and lymphoid and nonlymphoid) as well as in novel models recently being utilized in the field of toxicology. These methods can be used for current testing and to determine mechanisms by which a xenobiotic can cause immunotoxicity.