A systematic review of provocation studies of persons reporting multiple chemical sensitivities (MCS) was conducted from databases searched from inception to May 2006. Thirty-seven studies were identified, testing 784 persons reporting MCS, 547 control subjects, and 180 individuals of whom a subset were chemically sensitive. Blinding was inadequate in most studies. In 21 studies odors of chemicals were probably apparent; 19 of these reported positive responses to provocations among chemically sensitive individuals, and 1 study demonstrated that negative expectations were significantly associated with increased symptom reporting after provocations. Seven studies used chemicals at or below odor thresholds, and 6 failed to show consistent responses among sensitive individuals after active provocation. Six studies used forced-choice discrimination and demonstrated that chemically sensitive individuals were not better at detecting odor thresholds than nonsensitive participants. Three studies tested individuals by using nose clips/face masks and confirmed response, possibly mediated through eye exposure. Three studies used olfactory masking agents to conceal stimuli, and none of these found associations between provocations and response. We conclude that persons with MCS do react to chemical challenges; however, these responses occur when they can discern differences between active and sham substances, suggesting that the mechanism of action is not specific to the chemical itself and might be related to expectations and prior beliefs.