The aim of this study was to evaluate the relationships between blood lactate and plasma glucose, insulin (IRI) and C-peptide (IRCP) during the first hour of an oral glucose load (OGTT, 100 g). Twelve controls, sixteen non-insulin-dependent (NIDDM) and four insulin-dependent (IDDM) diabetic subjects were studied. A significant increase in blood lactate was observed at 15 min in normal subjects, whereas there was a delayed increase at 45 min in NIDDM subjects, in the presence of IRCP increments of 0.31 nmol/l. In order to have a minimum significant lactate increment, the threshold value of peripheral IRCP increment was about 0.30 nmol/l. In IDDM subjects, despite considerable hyperglycemia, blood lactate concentration remained unchanged throughout the test. In normal and NIDDM subjects there was a significant negative correlation between delta lactate and delta glucose (r = -0.89, p less than 0.001) and a significant positive correlation between delta lactate and delta IRCP (r = 0.78, p less than 0.001). In conclusion, hyperglycemia itself and the lack of increase in insulin secretion do not affect blood lactate increase during OGTT; blood concentration of this metabolite depends mainly on an early insulin secretion apt to enhance tissue glucose uptake and to inhibit gluconeogenesis.