Multiple chemical sensitivities (MCS) has become an increasingly frequent diagnosis assigned to patients with symptoms associated with exposures to environmental chemicals, Since the characteristic symptoms of MCS are triggered by very low concentrations of chemicals, in the range of olfactory thresholds, it is widely believed that the intranasal chemoreceptive senses are involved in the pathophysiology of MCS. Thus, the present study addressed both the olfactory and trigeminal systems; using a double-blind approach we investigated whether MCS patients show differences in responses after exposure to either room air or low concentrations of a widely used chemical agent (a-propanol). A total of 23 patients participated in the experiments (mean age 47 years; 13 female, 10 male). MCS was diagnosed according to Cullen's criteria. Performance of the nasal chemical senses was established by means of chemosensory event-related potentials (CSERP) and subjective measures of olfactory function (odor discrimination, phenylethyl alcohol odor thresholds). CSERP were recorded in response to olfactory (H2S), and trigeminal (CO2) stimuli, The study provided three major results: (1) Approximately 20% of patients diagnosed with MCS presented symptoms regardless of the type of challenge, suggesting the susceptibility of MCS patients to unspecific experimental manipulations. (2) Changes in CSERP latencies indicated a change in the processing of both olfactory and trigeminal stimuli, (3) While odor thresholds remained unchanged, the patients' ability to discriminate odors decreased after exposure to room air, In contrast, this decrease was less pronounced after exposure to 2-prop. Summarily, MCS patients respond to challenge with a-prop with changes of chemosensory perception which might increase their susceptibility to environmentally volatile chemicals. Changes in the pattern of event-related potentials are interpreted as the possible change of the orientation of cortical generators, i.e., neuronal populations that were involved in the processing of chemosensory information. However, investigations in healthy controls are needed in order to draw further conclusions. (C) 1996 Academic Press, Inc.