Idiopathic environmental intolerance (IEI) is a medically unexplained disorder characterised by a wide variety of unspecific symptoms in different organ systems and attributed to nontoxic concentrations of chemicals and other environmental factors that are tolerated by the majority of individuals. Both exposure to chemicals and behavioural conditioning are considered as possible contributors to the development of IEI. However, owing to the heterogeneity of the condition, it is difficult to separate the toxicological, physiological and psychological aspects of IEI. Here, we review the evidence for postulated toxicologically mediated mechanisms for IEI. Available data do not support either a classical receptor-mediated or an idiosyncratic toxicological mechanism. Furthermore, if there were convincing evidence for a psychological cause for many patients with IEI, then this would suggest that the priority for the future is the development of psychological treatments for IEI. Finally, we advocate genome wide screening of IEI patients to elucidate genotypic features of the condition.