Immunologic abnormalities have long been advanced as a potential mechanism for multiple chemical sensitivity (MCS). An immunologic mechanism is supported in part by the systemic nature of the symptoms reported, the complex interactions known to exist between the immune system and other systems, and limited experimental evidence. However, there are both theoretical grounds for doubting an immunologic mechanism in MCS and methodological constraints in many of the studies that have been conducted in humans. The authors discuss the structure and function of the immune system as it potentially applies to MCS, the uses and limitations of immunologic testing, and the evidence for immunologic theories of MCS. They describe recent work to validate some of the immunologic tests used in MCS and consider opportunities for further research.