We investigated the effects of infusion of a 20% triglyceride emulsion plus heparin (LH) on carbohydrate (CHO) metabolism during basal insulin and glucose turnover conditions in normal male subjects. In study 1, LH or saline was infused at 0.5 and 1.5 ml/min for 2 h each. Plasma free fatty acids rose from ∼0.4 to 0.8 mM with the low rate and to between 1.6 and 2.1 mM with the high rate. Similar increases occurred in plasma concentrations of glycerol, acetoacetate, and β-hydroxybutyrate. LH infusions resulted in significant increases in C-peptide concentrations but had no effects on any of the other measured parameters of CHO metabolism. In study 2, LH or saline was infused as in study 1, but the compensatory insulin release was prevented by intravenous infusion of somatostatin and replacement of basal insulin and glucagon concentrations. This resulted in significant increases in plasma glucose (from 4.5 ± 0.2 to 7.1 ± 0.6 mM, P < 0.001) and hepatic glucose output (from 9.0 ± 1.5 to 11.3 ± 1.4 μmol · kg⁻¹ · min⁻¹, P < 0.05) and a decrease in glucose clearance (from 2.32 ± 0.13 to 1.44 ± 0.11 ml · kg⁻¹ · min⁻¹, P < 0.05). We conclude that lipids can have adverse effects on CHO metabolism under basal conditions and that healthy individuals can compensate for these effects with additional secretion of insulin.