In order to examine whether hyperinsulinaemia induced glucocorticoid therapy involves alterations of the enteroinsular axis glucose, insulin, C-peptide, glucagon and GIP responses to a test meal with and without prior intake of dexamethasone (2 + 2 mg) in 13 healthy subjects were measured. Dexamethasone caused impaired glucose tolerance, which was associated with an exaggerated insulin (0.61 +/- 0.05 vs. 0.38 +/- 0.05 nmol/l; p less than 0.001). C-peptide (0.97 +/- 0.08 vs. 0.71 +/- 0.06 nmol/l; p less than 0.001) and glucagon response to a test meal. In contrast, the GIP response to the test meal was blunted after dexamethasone (126 +/- 17 vs. 177 +/- 23 pmol/l; p less than 0.001). It therefore follows that alterations in the enteroinsular axis, that is, GIP secretion, cannot be responsible for the enhancement of insulin secretion observed after dexamethasone. The mechanism(s) for the decreased GIP response after dexamethasone could involve (1) a direct inhibitory effect on GIP secretion by dexamethasone, and/or (2) a negative feedback of elevated glucose and insulin levels on GIP secretion.