The short synacthen test (SST) is an effective method of assessing the hypothalamo-pituitary-adrenal (HPA) axis in patients with pituitary disease. Chronic glucocorticoid therapy may result in suppression of the HPA axis, and use of the SST has not been evaluated in these patients. This study compares the SST with the insulin tolerance test (ITT) in patients on long-term corticosteroid therapy. Both tests were done on 22 patients on long-term, stable-dose prednisolone (< 10 mg/day). A pass was defined as a 30 minute plasma cortisol > 550 nmol/l for the SST and a maximal cortisol of > 500 nmol/l for the ITT. Five patients passed both tests; nine failed both. Eight patients had discrepant results; all passed the ITT but failed the SST. There was a significant correlation (p < 0.001) between the maximum cortisol level achieved during the ITT and the 30 min SST value and the incremental rise. There was an inverse correlation between the dose and duration of use of steroids and the cortisol response during both tests. The SST is a reliable, safe and easily performed initial assessment of the HPA axis in patients on long-term corticosteroids. The ITT remains a valuable test for those who fail the SST.