The aim of the present study was to characterize the effect of 44 h of hyperglycaemia on diurnal levels of insulin-like growth factor binding protein-1 (IGFBP-1), insulin-like growth factor-1 (IGF-1), growth hormone (GH) and glucagon in 7 well-controlled subjects with insulin-dependent diabetes mellitus (IDDM). Hyperglycaemia (approximately 15 mmol/l) was induced by a glucose infusion, while the degree of insulinisation was similar to that of a corresponding period with near normoglycaemia (approximately 6.9 mmol/l). Hyperglycaemia for 44 h did not alter the normal diurnal IGFBP-1 levels when the degree of insulinisation was unchanged. The diurnal secretion pattern of IGFBP-1 was preserved in both genders and without any difference between the control and hyperglycaemic periods. However, the IGFBP-1 levels were increased in these IDDM subjects despite a peripheral hyperinsulinemia. An inverse correlation was found between IGFBP-1 and peripheral insulin levels both during periods of rapid changes in IGFBP-1 and insulin concentrations (i.e. morning hours) as well as during the total 24-h sampling period. Total IGF-1 levels were low, but no further decrease was seen after 24 h of hyperglycaemia in the presence of unchanged insulin levels. In conclusion, the present study clearly shows that the increased IGFBP-1 level seen during poor metabolic control in IDDM is not caused by hyperglycaemia. Glucose levels per se do not influence either total IGF-1 or IGFBP-1 concentrations in well-insulinised diabetic patients.