Glucocorticoid (GC) sensitivity varies considerably in healthy controls as well as in patients with chronic inflammatory diseases like multiple sclerosis (MS). We investigated whether polymorphisms in the glucocorticoid receptor (N363S, ER22/23EK, and the BclI) were responsible for altered GC sensitivity. In healthy controls we found an association between the N363S allele of the GR and a reduced peripheral GC sensitivity. In MS patients neither the variant N363S, the BclI RFLP nor the ER22/23EK allele were found to be associated with GC sensitivity. GC sensitivity is probably in part genetically influenced in healthy controls, but in MS patients other factors seem to have more impact on GC sensitivity.