The serum levels of the low molecular form of insulin-like growth factor binding protein (IGFBP) was determined in 56 outpatients with diabetes mellitus by a radioimmunoassay developed for amniotic 35 kDa IGFBP. The mean level of 35 kDa IGFBP was found to be threefold higher in insulin dependent diabetes mellitus (IDDM), 112 +/- 13 ng/ml, than in age matched controls, 37 +/- 2 ng/ml, while the mean level in non-insulin dependent diabetes mellitus (NIDDM), 16 +/- 2 ng/ml, was decreased. In hospitalized IDDM patients there was a significant correlation (r = 0.91, p less than 0.01) between fasting blood-glucose and 35 kDa IGFBP levels, not found in NIDDM patients. During insulin infusion the 35 kDa IGFBP levels declined with a half-life of 60-120 min. The decline in IGFBP continued even after the establishment of steady state B-glucose at 4.7 mmol/l. In conclusion, the elevated 35 kDa IGFBP levels in IDDM can be attributed to insulin deficiency and may reflect a reduced bioavailability of the IGFs at the target cells.