SummaryWe studied the effect of hyperviscosity on plasma glucose concentration, endogenous glucose production, and plasma insulin concentration in 12 term mixed breed newborn lambs. After a 7-hr fast, 0.45% saline was infused at a constant rate for 6 hr during which time hourly plasma glucose and 3-hourly plasma insulin concentrations were determined. A glucose turnover determination by the prime-constant infusion technique using3H6radiolabeled glucose was performed at a steady state. An exchange transfusion was then carried out using maternal packed red blood cells in six lambs to produce hyperviscosity and using maternal whole blood in six other lambs to maintain normoviscosity. After the exchange transfusion, a second study identical to that in the pre-exchange period was carried out. There was no significant difference in the mean plasma glucose concentration (mg/dl; mean ± S.E.) between groups during the first turnover period (pre-exchange transfusion) [103 ± 4.9 (Normoviscous)versus96 ± 4.8 (Hyperviscous)), but during the postexchange transfusion turnover period, the plasma glucose concentration was lower in the hyperviscous than in the normoviscous group [89 ± 4.3 (Normoviscous)versus76 ± 4.0 (Hyperviscous)] (P<0.05.) Endogenous glucose production declined from the first to the second glucose turnover determination in both groups, but there was no significant difference between the normoviscous and hyperviscous groups. Plasma insulin concentrations were similarly low in both groups suggesting suppression in the fasted state. The data suggest that the hyperviscosity acts as an independent variable to depress plasma glucose concentration, the mechanism of which is still undefined.