Glucocorticoid-induced glucose intolerance and insulin resistance are dependent on the type of steroid, its dose and route of administration. Although the intravenous (i.v.) route is used mainly, the effects of different steroids have so far been compared using the oral route. The present study was therefore planned to compare the effects on glucose metabolism of hydrocortisone (HC) and methylprednisolone (MP) administered i.v. at equivalent antiinflammatory doses in healthy subjects. Eighteen healthy volunteers with normal glucose tolerance, divided into three groups (A,B,C) matched for age, sex and body mass index were subjected to oral glucose tolerance tests (oGTT) 12 h after HC or MP i.v. injection. The two tests were performed at a 1-month interval and in random sequence. Group A received low doses (HC 100 mg, MP 20 mg), group B intermediate doses (HC 200 mg, MP 40 mg) and group C high doses (HC 400 mg, MP 80 mg). Serum glucose, insulin and C-peptide were measured during both fasting and oGTT. Serum glucose values were not significantly different after HC or MP, during both fasting and oGTT. However, there was a positive correlation between fasting serum glucose or the area under the glucose curve and the dose.kg-1 body weight of HC (r = 0.748; r = 0.462) and MP (r = 0.708; r = 0.736). Serum insulin values were significantly higher after MP than after HC when fasting (A: 115 vs 223; B: 95 vs 215, C: 158 vs 268 pmol.l-1) and as area under the oGTT curve (A: 57.8 vs 87; B: 48.5 vs 92.1; C:57.8 vs 94.5 pmol.l-1 x 2 h).(ABSTRACT TRUNCATED AT 250 WORDS)